WO2015190586A1 - 大腸がんの検出キット又はデバイス及び検出方法 - Google Patents

大腸がんの検出キット又はデバイス及び検出方法 Download PDF

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WO2015190586A1
WO2015190586A1 PCT/JP2015/066970 JP2015066970W WO2015190586A1 WO 2015190586 A1 WO2015190586 A1 WO 2015190586A1 JP 2015066970 W JP2015066970 W JP 2015066970W WO 2015190586 A1 WO2015190586 A1 WO 2015190586A1
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mir
hsa
gene
seq
polynucleotide
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PCT/JP2015/066970
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English (en)
French (fr)
Japanese (ja)
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聡子 小園
信正　均
近藤　哲司
裕子 須藤
淳平 河内
淳志 落合
基寛 小嶋
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東レ株式会社
国立研究開発法人国立がん研究センター
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Priority to JP2016527884A priority Critical patent/JP6778107B2/ja
Priority to CN201580031244.9A priority patent/CN106661619B/zh
Priority to KR1020237008773A priority patent/KR102633955B1/ko
Priority to US15/318,312 priority patent/US10604810B2/en
Application filed by 東レ株式会社, 国立研究開発法人国立がん研究センター filed Critical 東レ株式会社
Priority to KR1020177000841A priority patent/KR102401688B1/ko
Priority to BR112016029090-9A priority patent/BR112016029090B1/pt
Priority to RU2017100884A priority patent/RU2017100884A/ru
Priority to EP21189691.5A priority patent/EP3971299A3/en
Priority to KR1020227016897A priority patent/KR102511713B1/ko
Priority to EP15806013.7A priority patent/EP3156499B1/en
Priority to KR1020247003646A priority patent/KR20240023185A/ko
Priority to CA2951127A priority patent/CA2951127A1/en
Publication of WO2015190586A1 publication Critical patent/WO2015190586A1/ja
Priority to US16/789,986 priority patent/US11479821B2/en
Priority to US17/945,243 priority patent/US20230104293A1/en

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Definitions

  • the present invention relates to a colorectal cancer detection kit or device containing a nucleic acid capable of specifically binding to a specific miRNA, which is used for examining whether or not a subject has colorectal cancer, and the nucleic acid.
  • the present invention relates to a method for detecting colorectal cancer, which comprises measuring the expression level of the miRNA using.
  • the large intestine is an organ that accumulates the remaining intestinal contents that have been digested and absorbed, and makes it stool while absorbing water.
  • the large intestine begins at the cecum and then leads to the ascending colon, transverse colon, descending colon, sigmoid colon, rectum, and anal canal.
  • the number of people with colorectal cancer is 112,772, that is, about the number of Japanese One in 14 people is said to suffer from colorectal cancer, and is the second most cancerous site.
  • the number of deaths from colorectal cancer is 45,744 for both men and women, and the number of deaths is the third highest cancer site.
  • Non-patent Document 1 In the United States, it is said that approximately one out of every 20 people will develop colorectal cancer, and the estimated number of people with colorectal cancer in the United States in 2014 reached 96,830, of which about 40,000. A person is said to die (Non-patent Document 1).
  • the degree of progression of colorectal cancer is defined in Non-Patent Document 2, and includes tumor spread (Tis, T1-T4), lymph node metastasis (N0, N1a-c, N2a-b), and distant metastasis (M0, M1a- b)
  • stage 0 Tis / N0 / M0
  • stage I T1 to T2 / N0 / M0
  • stage II T3 to T4 / N0 / M0
  • stage IIA T3 / N0 / M0
  • Stage IIB T4a / N0 / M0
  • Stage IIC T4b / N0 / M0
  • Stage III Stage III
  • Stage IIIA T1-2 / N1 / M0 and T1 / N2a / M0
  • Stage IIIB T3-T4a / N1 / M0 and T2-T3 / N2a / M0 and T1-T2 / N2
  • Non-Patent Document 1 reports the following statistical values for colon cancer and rectal cancer.
  • the 5-year relative survival rate for colon cancer is 74% for stage I, 67% for stage IIA, 59% for stage IIB, 37% for stage IIC, 73% for stage IIIA, 46% for stage IIIB, and 46% for stage IIIC. It is reported that 28% and stage IV is 6%.
  • the 5-year relative survival rate for rectal cancer is 74% for stage I, 65% for stage IIA, 52% for stage IIB, 32% for stage IIC, 74% for stage IIIA, 45% for stage IIIB, stage It is reported that IIIC is 33% and stage IV is 6%. From the above, colon cancer with a low degree of progression has a high survival rate. Therefore, if colorectal cancer can be detected and treated at an early stage, it will greatly contribute to the improvement of survival rate.
  • Non-patent Document 1 Treatment of colorectal cancer is mainly laparoscopic surgery or laparoscopic surgery, and anticancer drug treatment or radiation therapy is often used after surgery (Non-patent Document 1). Endoscopic surgery that can be treated without laparotomy may be indicated, especially for early colon cancer.
  • Non-Patent Document 1 fecal occult blood tests and endoscopy are widely used for colorectal cancer tests.
  • the American Cancer Society recommends that the fecal occult blood test be taken annually.
  • image examination such as enema contrast examination, CT examination, and MRI examination is performed.
  • blood tumor marker tests such as CEA and CA19-9 may be performed on patients who have already been diagnosed with colorectal cancer for the purpose of prognostic observation and therapeutic effect observation (Non-patent Document 1). .
  • Patent Document 1 describes colorectal cancer and other cancers using hsa-miR-92a-2-5p, hsa-miR-128-2-5p, and hsa-miR-24-3p in colorectal cancer tissues. How to detect is shown.
  • Patent Document 2 discloses a method for detecting colorectal cancer using hsa-miR-1233-5p or hsa-miR-1225-3p in plasma.
  • Patent Document 3 discloses a method for detecting colorectal cancer using a plurality of miRNAs such as hsa-miR-1231, hsa-miR-423-5p and hsa-miR-1268a in large intestine tissues and stool.
  • Patent Document 4 discloses a method for detecting colorectal cancer using hsa-miR-150-3p, miR-92a-2-5p, etc. in tissues.
  • An object of the present invention is to find a novel colorectal cancer tumor marker and provide a method capable of effectively detecting colorectal cancer using a nucleic acid capable of specifically binding to the marker.
  • the fecal occult blood test which is currently widely used as the primary test for colorectal cancer, is determined to be positive even when bleeding for reasons other than cancer such as sputum, while early colorectal cancer without bleeding. There is also a report that 90% or more of colon abnormalities (including cancer) are missed (Non-patent Document 1).
  • Non-patent Document 3 Specific sensitivity of the fecal occult blood test varies greatly from 37% to 79.4% depending on the test kit used, and the specificity is set to 86.7% to 97.7% (Non-patent Document 3).
  • colonoscopy is known to have high inspection accuracy, it is difficult to apply to primary screening due to the necessity of pretreatment and sedatives and relatively high price (Non-patent Document 1). ).
  • blood tumor markers such as CEA and CA19-9 may be elevated even in cancers other than colorectal cancer, so it is said that the presence or absence of colorectal cancer cannot be determined.
  • Non-patent Document 1 the specificity of the CEA test is 99%, while the sensitivity is only 12%, and the significance of tumor marker measurement as a colorectal cancer screening test is considered to be poor (Non-patent Document 4).
  • microRNA microRNA
  • Patent Document 1 describes colorectal cancer and other cancers using hsa-miR-92a-2-5p, hsa-miR-128-2-5p, and hsa-miR-24-3p in colorectal cancer tissues. How to detect is shown. However, this detection method is not preferable as an examination method because it is necessary to obtain a colorectal cancer tissue specimen by surgery, and this process places a heavy physical burden on the patient. In addition, since this detection method has no description of colorectal cancer detection performance such as specific accuracy, sensitivity, and specificity, it is poor in industrial practicality.
  • Patent Document 3 discloses a method for detecting colorectal cancer using a plurality of miRNAs such as hsa-miR-1231, hsa-miR-423-5p and hsa-miR-1268a in large intestine tissue and stool.
  • miRNAs such as hsa-miR-1231, hsa-miR-423-5p and hsa-miR-1268a in large intestine tissue and stool.
  • performing a surgical operation to obtain colorectal cancer tissue is not preferable as an inspection method because the physical burden imposed on the patient is heavy.
  • the stool specimen is non-invasively collected, there is a problem that the test substance may be present unevenly in the stool and the test results are likely to vary.
  • Patent Document 4 discloses a method for detecting colorectal cancer using hsa-miR-150-3p, miR-92a-2-5p, etc. in tissues. Detection of accuracy, sensitivity, specificity, etc. There is no description about the performance, and since there is no description of a specific method for distinguishing colorectal cancer using blood, industrial utility is poor. Furthermore, since the miRNA marker has not been verified in an independent sample group, it lacks reliability.
  • the performance of existing tumor markers is low, or the performance and detection methods are not specifically shown for markers at the research stage. May cause a wasteful additional test by misdetecting a healthy body as a colorectal cancer patient, or a loss of treatment opportunity by overlooking a colorectal cancer patient.
  • measuring tens to hundreds of miRNAs increases the cost of testing, and is therefore difficult to use for large-scale screening such as medical examinations.
  • collecting colon tissue to measure tumor markers is not preferable because it is highly invasive to patients and can be detected from blood that can be collected in a minimally invasive manner. There is a need for a highly accurate colorectal cancer marker that can correctly distinguish a healthy body from a healthy body.
  • the present inventors have found a plurality of genes that can be used as detection markers for colorectal cancer from blood that can be collected in a minimally invasive manner, and a nucleic acid that can specifically bind to this gene. By using it, it was found that colorectal cancer can be detected significantly, and the present invention has been completed.
  • the present invention has the following features.
  • miR-6726-5p is hsa-miR-6726-5p
  • miR-4257 is hsa-miR-4257
  • miR-6787-5p is hsa-miR-6787-5p
  • miR-6780b -5p is hsa-miR-6780b-5p
  • miR-3131 is hsa-miR-3131
  • miR-7108-5p is hsa-miR-7108-5p
  • miR-13343-3p is hsa-miR -1343-3p
  • miR-1247-3p is hsa-miR-1247-3p
  • miR-4651 is hsa-miR-4651
  • miR-6757-5p is hsa-miR-6757-5p
  • MiR-3679-5p is hsa-miR-3679-5p and miR-7 41 is hsa-miR-7641,
  • MiR-4442 is hsa-miR-4442, miR-4433-3p is hsa-miR-4433-3p, miR-4707-5p is hsa-miR-4707-5p, and miR-6126 is hsa-miR-6126, miR-4449 is hsa-miR-4449, miR-4706 is hsa-miR-4706, miR-1913 is hsa-miR-1913, and miR-602 is hsa- miR-602, miR-939-5p is hsa-miR-939-5p MiR-4695-5p is hsa-miR-4695-5p, miR-711 is hsa-miR-711, miR-6816-5p is hsa-miR-6816-5p, and miR-4632 -5p is hsa-miR-4632-5p, miR-6721-5
  • the kit is another colorectal cancer marker, miR-1231, miR-1233-5p, miR-150-3p, miR-1225-3p, miR-92a-2-5p, miR-423- (1) to (1) further comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of 5p, miR-1268a, miR-128-2-5p and miR-24-3p.
  • the kit according to any one of 3).
  • miR-1231 is hsa-miR-1231
  • miR-1233-5p is hsa-miR-1233-5p
  • miR-150-3p is hsa-miR-150-3p
  • miR-1225 -3p is hsa-miR-1225-3p
  • miR-92a-2-5p is hsa-miR-92a-2-5p
  • miR-423-5p is hsa-miR-423-5p
  • miR ⁇ 1268a is hsa-miR-1268a
  • miR-128-2-5p is hsa-miR-128-2-5p
  • miR-24-3p is hsa-miR-24-3p
  • the kit is another colorectal cancer marker, miR-4697-5p, miR-3197, miR-675-5p, miR-4486, miR-7107-5p, miR-23a-3p, miR- At least one polynucleotide selected from the group consisting of 4667-5p, miR-451a, miR-3940-5p, miR-8059, miR-6683-5p, miR-4492, miR-4476 and miR-6090;
  • the kit according to any one of (1) to (6), further comprising a nucleic acid capable of specifically binding.
  • miR-4697-5p is hsa-miR-4697-5p
  • miR-3197 is hsa-miR-3197
  • miR-675-5p is hsa-miR-675-5p
  • miR-4486 Is hsa-miR-4486
  • miR-7107-5p is hsa-miR-7107-5p
  • miR-23a-3p is hsa-miR-23a-3p
  • miR-4667-5p is hsa-miR -4667-5p
  • miR-451a is hsa-miR-451a
  • miR-3940-5p is hsa-miR-3940-5p
  • miR-8059 is hsa-miR-8059
  • miR-6683 -5p is hsa-miR-6913-5p
  • miR-4492 is hsa-miR-6913-5p
  • the kit according to any one of (1) to (9), comprising the nucleic acid of (1) comprising the nucleic acid of (1).
  • miR-6726-5p is hsa-miR-6726-5p
  • miR-4257 is hsa-miR-4257
  • miR-6787-5p is hsa-miR-6787-5p
  • miR-6780b -5p is hsa-miR-6780b-5p
  • miR-3131 is hsa-miR-3131
  • miR-7108-5p is hsa-miR-7108-5p
  • miR-13343-3p is hsa-miR -1343-3p
  • miR-1247-3p is hsa-miR-1247-3p
  • miR-4651 is hsa-miR-4651
  • miR-6757-5p is hsa-miR-6757-5p
  • MiR-3679-5p is hsa-miR-3679-5p
  • miR- 641 is hsa-miR-76
  • MiR-4442 is hsa-miR-4442, miR-4433-3p is hsa-miR-4433-3p, miR-4707-5p is hsa-miR-4707-5p, and miR-6126 is hsa-miR-6126, miR-4449 is hsa-miR-4449, miR-4706 is hsa-miR-4706, miR-1913 is hsa-miR-1913, and miR-602 is hsa- miR-602 and miR-939-5p is hsa-miR-939-5 p, miR-4695-5p is hsa-miR-4695-5p, miR-711 is hsa-miR-711, miR-6816-5p is hsa-miR-6816-5p, miR- 4632-5p is hsa-miR-4632-5p, miR-6721
  • the device is another colorectal cancer marker, miR-1231, miR-1233-5p, miR-150-3p, miR-1225-3p, miR-92a-2-5p, miR-423- (11) to (11) further comprising a nucleic acid capable of specifically binding to at least one or more polynucleotides selected from the group consisting of 5p, miR-1268a, miR-128-2-5p and miR-24-3p.
  • the device according to any one of 13).
  • miR-1231 is hsa-miR-1231
  • miR-1233-5p is hsa-miR-1233-5p
  • miR-150-3p is hsa-miR-150-3p
  • miR-1225 -3p is hsa-miR-1225-3p
  • miR-92a-2-5p is hsa-miR-92a-2-5p
  • miR-423-5p is hsa-miR-423-5p
  • miR ⁇ 1268a is hsa-miR-1268a
  • miR-128-2-5p is hsa-miR-128-2-5p
  • miR-24-3p is hsa-miR-24-3p
  • the device is another colorectal cancer marker, miR-4697-5p, miR-3197, miR-675-5p, miR-4486, miR-7107-5p, miR-23a-3p, miR- At least one polynucleotide selected from the group consisting of 4667-5p, miR-451a, miR-3940-5p, miR-8059, miR-6683-5p, miR-4492, miR-4476 and miR-6090;
  • the device according to any one of (11) to (16), further comprising a nucleic acid capable of specifically binding.
  • miR-4697-5p is hsa-miR-4697-5p
  • miR-3197 is hsa-miR-3197
  • miR-675-5p is hsa-miR-675-5p
  • miR-7107-5p is hsa-miR-7107-5p
  • miR-23a-3p is hsa-miR-23a-3p
  • miR-4667-5p is hsa-miR -4667-5p
  • miR-451a is hsa-miR-451a
  • miR-3940-5p is hsa-miR-3940-5p
  • miR-8059 is hsa-miR-8059
  • miR-6683 -5p is hsa-miR-6913-5p and miR-4492 is hsa-miR Is 4492, miR-44
  • the device comprises at least two or more nucleic acids capable of specifically binding to each of at least two or more polynucleotides selected from all the colon cancer markers according to (11) or (12). The device according to any one of (11) to (21).
  • polynucleotide is used for nucleic acids including RNA, DNA, and RNA / DNA (chimera).
  • the DNA includes any of cDNA, genomic DNA, and synthetic DNA.
  • the RNA includes total RNA, mRNA, rRNA, miRNA, siRNA, snoRNA, snRNA, non-coding RNA and synthetic RNA.
  • synthetic DNA and “synthetic RNA” are artificially generated using, for example, an automatic nucleic acid synthesizer based on a predetermined base sequence (which may be either a natural sequence or a non-natural sequence). It refers to the prepared DNA and RNA.
  • non-natural sequence is intended to be used in a broad sense, and is a sequence (for example, one or more nucleotide substitutions, deletions, insertions and / or additions) that differs from the natural sequence ( That is, it includes a mutant sequence), a sequence containing one or more modified nucleotides (ie, a modified sequence), and the like.
  • the polynucleotide is used interchangeably with the nucleic acid.
  • a “fragment” is a polynucleotide having a base sequence of a continuous part of a polynucleotide, and desirably has a length of 15 bases or more, preferably 17 bases or more, more preferably 19 bases or more. .
  • RNA and double-stranded DNA include not only RNA and double-stranded DNA, but also each single-stranded DNA such as positive strand (or sense strand) or complementary strand (or antisense strand) constituting the same. It is intended to be used.
  • the length is not particularly limited.
  • “gene” refers to double-stranded DNA containing human genomic DNA, single-stranded DNA containing cDNA (positive strand), and single-stranded DNA having a sequence complementary to the positive strand.
  • DNA complementary strand
  • miRNA microRNA
  • transcripts fragments thereof, and transcripts are all included.
  • the “gene” is not limited to a “gene” represented by a specific nucleotide sequence (or sequence number), but also RNAs having biological functions equivalent to RNA encoded by these, for example, homologs (ie, homologs). Or orthologs), variants such as genetic polymorphisms, and “nucleic acids” encoding derivatives.
  • the “nucleic acid” encoding the homologue, variant or derivative is, for example, the base sequence represented by any of SEQ ID NOs: 1 to 635 under the stringent conditions described later, or the base A “nucleic acid” having a base sequence that hybridizes with a complementary sequence of the base sequence in which u is t in the sequence can be mentioned.
  • the “gene” does not ask whether the functional region is different, and may include, for example, an expression control region, a coding region, an exon, or an intron. Further, the “gene” may be contained in the cell, may be released outside the cell and may be present alone, or may be encapsulated in a vesicle called an exosome.
  • exosome is a vesicle encased in a lipid bilayer secreted from a cell. Exosomes are derived from multivesicular endosomes, and when released to the extracellular environment, they may contain biological substances such as “genes” such as RNA and DNA and proteins. It is known that exosomes are contained in body fluids such as blood, serum, plasma and lymph.
  • RNA refers to RNA synthesized using a DNA sequence of a gene as a template.
  • RNA is synthesized in such a manner that RNA polymerase binds to a site called a promoter located upstream of the gene and ribonucleotides are bound to the 3 'end so as to be complementary to the DNA base sequence.
  • This RNA includes not only the gene itself but also the entire sequence from the transcription start point to the end of the poly A sequence, including the expression control region, coding region, exon or intron.
  • microRNA is a protein complex that is transcribed as a hairpin-like RNA precursor, cleaved by a dsRNA cleaving enzyme having RNase III cleaving activity, and called RISC. 15-25 base non-coding RNA that is incorporated into and is involved in the translational repression of mRNA.
  • miRNA is not limited to “miRNA” represented by a specific nucleotide sequence (or sequence number), but also a precursor of the “miRNA” (pre-miRNA, pri-miRNA), and these And miRNAs that have equivalent biological functions, such as homologs (ie, homologs or orthologs), variants such as genetic polymorphisms, and derivatives. Such precursors, homologues, mutants or derivatives can be specifically identified by miRBase release 20 (http://www.mirbase.org/) under stringent conditions described later. And “miRNA” having a base sequence that hybridizes with a complementary sequence of any one of the specific base sequences represented by any of SEQ ID NOs: 1 to 635.
  • miRNA used herein may be a gene product of a miR gene, and such a gene product is a mature miRNA (for example, 15 to 15 involved in the suppression of translation of mRNA as described above). 25-base, or 19-25 base non-coding RNA) or miRNA precursors (eg, pre-miRNA or pri-miRNA as described above).
  • the “probe” includes a polynucleotide used for specifically detecting RNA produced by gene expression or a polynucleotide derived therefrom and / or a polynucleotide complementary thereto.
  • the “primer” includes a polynucleotide that specifically recognizes and amplifies RNA generated by gene expression or a polynucleotide derived therefrom and / or a polynucleotide complementary thereto.
  • a complementary polynucleotide is a polynucleotide comprising a base sequence defined by any of SEQ ID NOs: 1 to 635 or a base sequence in which u is t in the base sequence.
  • the base sequence is complementary to the full-length sequence or a partial sequence thereof (for convenience, this is referred to as the positive strand) based on the base pair relationship such as A: T (U), G: C.
  • such a complementary strand is not limited to the case where it forms a completely complementary sequence with the target positive strand base sequence, but has a complementary relationship that allows hybridization with the target normal strand under stringent conditions. There may be.
  • stringent conditions refers to the degree to which a nucleic acid probe is larger than other sequences (for example, the average of background measurement values + standard error of background measurement values ⁇ 2 or more measurement values) The conditions for hybridizing to the target sequence. Stringent conditions are sequence-dependent and depend on the environment in which hybridization is performed. By controlling the stringency of the hybridization and / or wash conditions, target sequences that are 100% complementary to the nucleic acid probe can be identified. Specific examples of “stringent conditions” will be described later.
  • the “Tm value” means a temperature at which the double-stranded portion of the polynucleotide is denatured into a single strand and the double strand and the single strand are present at a ratio of 1: 1.
  • variant refers to a natural variant caused by polymorphism, mutation, etc., or any one of the nucleotide sequences of SEQ ID NOs: 1 to 194 and 606 to 614, or the base in the case of nucleic acid.
  • “several” means an integer of about 10, 9, 8, 7, 6, 5, 4, 3 or 2.
  • a mutant can be prepared using a well-known technique such as site-directed mutagenesis or PCR-based mutagenesis.
  • % identity can be determined using the above-described BLAST or FASTA protein or gene search system with or without introducing a gap (Zheng Zhang et al., 2000, J. Comput. Biol., 7, p203-214; Altschul, SF et al., 1990, Journal of Molecular Biology, 215, p403-410; Pearson, WR et al., 1988. Proc. Natl. Acad. Sci. USA, vol.85, pp. 2444-2448).
  • the term “derivative” refers to a modified nucleic acid, a non-limiting group such as a labeled derivative such as a fluorophore, a modified nucleotide (for example, a halogen, an alkyl such as methyl, an alkoxy such as methoxy, a group such as thio, carboxymethyl, etc.
  • a derivative containing PNA peptide nucleic acid; Nielsen, PE, etc.). 1991, Science, 254, p1497-500
  • LNA locked nucleic acid; Obika, S. et al., 1998, Tetrahedron Lett., 39, p5401-5404) and the like.
  • the “nucleic acid” capable of specifically binding to a polynucleotide selected from the above-mentioned colorectal cancer marker miRNA is a synthesized or prepared nucleic acid, specifically, “nucleic acid probe” or “In order to detect the presence or absence of colorectal cancer in a subject, including the presence or absence of colorectal cancer, the degree of morbidity, whether or not colorectal cancer has been improved or improved, colorectal cancer It is directly or indirectly used for diagnosing susceptibility to treatment, or for screening candidate substances useful for prevention, amelioration or treatment of colorectal cancer.
  • nucleotides, oligonucleotides and polynucleotides capable of binding are used as probes for detecting the gene expressed in vivo, in tissues or cells based on the above properties, and for amplifying the gene expressed in vivo. It can be effectively used as a primer.
  • nucleic acid probe or primer used in the present invention binds to a specific target nucleic acid and cannot substantially bind to another nucleic acid.
  • the term “detection” can be replaced by the term inspection, measurement, detection or decision support. Further, in this specification, the term “evaluation” is used in a meaning including supporting diagnosis or evaluation based on a test result or a measurement result.
  • subject includes humans, primates including chimpanzees, pet animals such as dogs and cats, livestock animals such as cows, horses, sheep and goats, rodents such as mice and rats, etc. Means a mammal.
  • healthy body also means an animal that is such a mammal and does not suffer from the cancer to be detected.
  • P or “P value” refers to the probability that, in a statistical test, a statistic more extreme than the statistic actually calculated from the data under the null hypothesis is observed. Indicates. Therefore, it can be considered that the smaller the “P” or “P value”, the more significant the difference between the comparison objects.
  • sensitivity means a value of (number of true positives) / (number of true positives + number of false negatives). High sensitivity makes it possible to detect colorectal cancer at an early stage, leading to complete removal of the cancerous part and a reduction in the recurrence rate.
  • specificity means (number of true negatives) / (number of true negatives + number of false positives). If the specificity is high, it is possible to prevent unnecessary additional tests by misidentifying a healthy body as a colorectal cancer patient, leading to reduction of the burden on the patient and reduction of medical costs.
  • accuracy means a value of (number of true positives + number of true negatives) / (number of all cases). The accuracy indicates the rate at which the discrimination results for all the samples are correct, and is a first index for evaluating the detection performance.
  • the “specimen” to be determined, detected or diagnosed changes the expression of the gene of the present invention as the colorectal cancer develops, the colorectal cancer progresses, and the therapeutic effect on the colorectal cancer is exhibited.
  • tissue and biomaterial Specifically, colon tissue and surrounding vessels, lymph nodes and organs, organs suspected of metastasis, skin, and body fluids such as blood, urine, saliva, sweat, and tissue exudates, and serum and plasma prepared from blood Others include stool and hair. Furthermore, it refers to a biological sample extracted from these, specifically genes such as RNA and miRNA.
  • hsa-miR-6726-5p gene or “hsa-miR-6726-5p” refers to the hsa-miR-6726-5p gene described in SEQ ID NO: 1 (miRBase Accession No. MIMAT0027353) and other species homologs or orthologs.
  • the hsa-miR-6726-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6726-5p “hsa-mir-6726” (miRBase Accession No. MI0022571, SEQ ID NO: 195) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4257 gene or “hsa-miR-4257” refers to the hsa-miR-4257 gene (miRBase Accession No. MIMAT0016878) described in SEQ ID NO: 2 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-4257 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192.
  • hsa-miR-4257 is known as “hsa-mir-4257” (miRBase Accession No. MI0015856, SEQ ID NO: 196) having a hairpin-like structure as a precursor.
  • hsa-miR-6787-5p gene or “hsa-miR-6787-5p” refers to the hsa-miR-6787-5p gene (miRBase Accession No. 3) described in SEQ ID NO: 3. MIMAT0027474) and other species homologs or orthologs.
  • the hsa-miR-6787-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6787-5p “hsa-mir-6787” (miRBase Accession No. MI0022632, SEQ ID NO: 197) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6780b-5p gene or “hsa-miR-6780b-5p” refers to the hsa-miR-6780b-5p gene (miRBase Accession No. 4) described in SEQ ID NO: 4. MIMAT0027572) and other species homologs or orthologs.
  • the hsa-miR-6780b-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6780b-5p” is known as “hsa-mir-6780b” (miRBase Accession No. MI0022681, SEQ ID NO: 198) having a hairpin-like structure as a precursor.
  • hsa-miR-3131 gene or “hsa-miR-3131” refers to the hsa-miR-3131 gene (miRBase Accession No. MIMAT0014996) described in SEQ ID NO: 5 or other species. Includes homologs or orthologs.
  • the hsa-miR-3131 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685.
  • “hsa-miR-3131” is known as “hsa-mir-3131” (miRBase Accession No. MI0014151, SEQ ID NO: 199) having a hairpin-like structure as a precursor.
  • hsa-miR-7108-5p gene or “hsa-miR-7108-5p” refers to the hsa-miR-7108-5p gene (miRBase Accession No. 5) described in SEQ ID NO: 6. MIMAT0028113) and other species homologs or orthologs.
  • the hsa-miR-7108-5p gene can be obtained by the method described in Ladwig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-7108-5p” is known as “hsa-mir-7108” (miRBase Accession No. MI0022959, SEQ ID NO: 200) having a hairpin-like structure as a precursor.
  • hsa-miR-1343-3p gene or “hsa-miR-1343-3p” refers to the hsa-miR-1343-3p gene (miRBase Accession No. 7) described in SEQ ID NO: 7. MIMAT0019776) and other species homologs or orthologs.
  • the hsa-miR-1343-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-1343-3p” “hsa-mir-1343” (miRBase Accession No. MI0017320, SEQ ID NO: 201) having a hairpin-like structure as a precursor is known.
  • hsa-miR-1247-3p gene or “hsa-miR-1247-3p” refers to the hsa-miR-1247-3p gene (miRBase Accession No. 8) described in SEQ ID NO: 8. MIMAT0022721) and other species homologs or orthologs.
  • the hsa-miR-1247-3p gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, 18, p610-621.
  • “hsa-miR-1247-3p” is known as “hsa-mir-1247” (miRBase Accession No. MI0006382, SEQ ID NO: 202) having a hairpin-like structure as a precursor.
  • hsa-miR-4651 gene or “hsa-miR-4651” refers to the hsa-miR-4651 gene (miRBase Accession No. MIMAT0019715) described in SEQ ID NO: 9 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-4651 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4651” is known as “hsa-mir-4651” (miRBase Accession No. MI0017279, SEQ ID NO: 203) having a hairpin-like structure as a precursor.
  • hsa-miR-6757-5p gene or “hsa-miR-6757-5p” refers to the hsa-miR-6757-5p gene (miRBase Accession No. 5) described in SEQ ID NO: 10. MIMAT0027414) and other species homologs or orthologs.
  • the hsa-miR-6757-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6757-5p “hsa-mir-6757” (miRBase Accession No. MI0022602, SEQ ID NO: 204) having a hairpin-like structure as a precursor is known.
  • hsa-miR-3679-5p gene or “hsa-miR-3679-5p” refers to the hsa-miR-3679-5p gene described in SEQ ID NO: 11 (miRBase Accession No. MIMAT0018104) and other species homologs or orthologs.
  • the hsa-miR-3679-5p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, 5, e9637.
  • “hsa-miR-3679-5p” is known as “hsa-mir-3679” (miRBase Accession No. MI0016080, SEQ ID NO: 205) having a hairpin-like structure as a precursor.
  • hsa-miR-7641 gene or “hsa-miR-7641” refers to the hsa-miR-7641 gene (miRBase Accession No. MIMAT0029782) described in SEQ ID NO: 12 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-7641 gene can be obtained by the method described in Yoo JK et al., 2013, Arch Pharm Res, 36, p353-358.
  • “Hsa-miR-7641” has a hairpin-like structure as its precursor, “hsa-mir-7464-1”, “hsa-mir-7641-2” (miRBase Accession No. MI0024975, MI0024976, SEQ ID NO: 206, 207) are known.
  • hsa-miR-6746-5p gene or “hsa-miR-6746-5p” refers to the hsa-miR-6746-5p gene described in SEQ ID NO: 13 (miRBase Accession No. MIMAT0027392) and other species homologs or orthologs.
  • the hsa-miR-6746-5p gene can be obtained by the method described in Ladwig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6746-5p” is known as “hsa-mir-6746” (miRBase Accession No. MI0022591, SEQ ID NO: 208) having a hairpin-like structure as a precursor.
  • hsa-miR-8072 gene or “hsa-miR-8072” refers to the hsa-miR-8072 gene (miRBase Accession No. MIMAT0030999) described in SEQ ID NO: 14 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-8072 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, 39, p480-487.
  • hsa-miR-8072 “hsa-mir-8072” (miRBase Accession No. MI0025908, SEQ ID NO: 209) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6741-5p gene or “hsa-miR-6741-5p” refers to the hsa-miR-6741-5p gene described in SEQ ID NO: 15 (miRBase Accession No. MIMAT0027383) and other species homologs or orthologs.
  • the hsa-miR-6741-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6741-5p” is known as “hsa-mir-6741” (miRBase Accession No. MI0022586, SEQ ID NO: 210) having a hairpin-like structure as a precursor.
  • hsa-miR-1908-5p gene or “hsa-miR-1908-5p” refers to the hsa-miR-1908-5p gene (miRBase Accession No. MIMAT0007881) and other species homologs or orthologs.
  • the hsa-miR-1908-5p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, 26, p2496-2505.
  • hsa-miR-1908-5p “hsa-mir-1908” (miRBase Accession No. MI0008329, SEQ ID NO: 211) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6857-5p gene or “hsa-miR-6857-5p” refers to the hsa-miR-6857-5p gene described in SEQ ID NO: 17 (miRBase Accession No. MIMAT0027614) and other species homologs or orthologs.
  • the hsa-miR-6857-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “Hsa-miR-6857-5p” is known as “hsa-mir-6857” (miRBase Accession No. MI0022703, SEQ ID NO: 212) having a hairpin-like structure as a precursor.
  • hsa-miR-4746-3p gene or “hsa-miR-4746-3p” refers to the hsa-miR-4746-3p gene described in SEQ ID NO: 18 (miRBase Accession No. MIMAT0019881) and other species homologs or orthologs.
  • the hsa-miR-4746-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4746-3p” is known as “hsa-mir-4746” (miRBase Accession No. MI0017385, SEQ ID NO: 213) having a hairpin-like structure as a precursor.
  • hsa-miR-744-5p gene or “hsa-miR-744-5p” refers to the hsa-miR-744-5p gene described in SEQ ID NO: 19 (miRBase Accession No. MIMAT0004945) and other species homologs or orthologs.
  • the hsa-miR-744-5p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, 16, p1299-1298.
  • hsa-miR-744-5p “hsa-mir-744” (miRBase Accession No. MI0005559, SEQ ID NO: 214) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4792 gene or “hsa-miR-4792” refers to the hsa-miR-4792 gene (miRBase Accession No. MIMAT0019964) described in SEQ ID NO: 20 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-4792 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • hsa-miR-4792 “hsa-mir-4792” (miRBase Accession No. MI0017439, SEQ ID NO: 215), which has a hairpin-like structure as a precursor, is known.
  • hsa-miR-564 gene or “hsa-miR-564” refers to the hsa-miR-564 gene (miRBase Accession No. MIMAT0003228) described in SEQ ID NO: 21 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-564 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, p3687-3692.
  • “hsa-miR-564” is known as “hsa-mir-564” (miRBase Accession No. MI0003570, SEQ ID NO: 216) having a hairpin-like structure as a precursor.
  • hsa-miR-6791-5p gene or “hsa-miR-6791-5p” refers to the hsa-miR-6791-5p gene described in SEQ ID NO: 22 (miRBase Accession No. MIMAT0027482) and other species homologs or orthologs.
  • the hsa-miR-6791-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6791-5p” is known as “hsa-mir-6791” (miRBase Accession No. MI0022636, SEQ ID NO: 217) having a hairpin-like structure as a precursor.
  • hsa-miR-6825-5p gene or “hsa-miR-6825-5p” refers to the hsa-miR-6825-5p gene described in SEQ ID NO: 23 (miRBase Accession No. MIMAT0027550) and other species homologs or orthologs.
  • the hsa-miR-6825-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6825-5p “hsa-mir-6825” (miRBase Accession No. MI0022670, SEQ ID NO: 218) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6826-5p gene or “hsa-miR-6826-5p” refers to the hsa-miR-6826-5p gene described in SEQ ID NO: 24 (miRBase Accession No. MIMAT0027552) and other species homologs or orthologs.
  • the hsa-miR-6826-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6826-5p “hsa-mir-6826” (miRBase Accession No. MI0022671, SEQ ID NO: 219) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4665-3p gene or “hsa-miR-4665-3p” refers to the hsa-miR-4665-3p gene described in SEQ ID NO: 25 (miRBase Accession No. MIMAT0019740) and other species homologs or orthologs.
  • the hsa-miR-4665-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4665-3p” is known as “hsa-mir-4665” (miRBase Accession No. MI0017295, SEQ ID NO: 220) having a hairpin-like structure as a precursor.
  • hsa-miR-4467 gene or “hsa-miR-4467” refers to the hsa-miR-4467 gene (miRBase Accession No. MIMAT0018994) described in SEQ ID NO: 26 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-4467 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • hsa-mir-4467 (miRBase Accession No. MI0016818, SEQ ID NO: 221) having a hairpin-like structure as a precursor is known.
  • hsa-miR-3188 gene or “hsa-miR-3188” refers to the hsa-miR-3188 gene (miRBase Accession No. MIMAT0015070) described in SEQ ID NO: 27 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-3188 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685.
  • hsa-miR-3188 “hsa-mir-3188” (miRBase Accession No. MI0014232, SEQ ID NO: 222) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6125 gene or “hsa-miR-6125” refers to the hsa-miR-6125 gene (miRBase Accession No. MIMAT0024598) described in SEQ ID NO: 28 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-6125 gene can be obtained by the method described in Smith JL et al., 2012, J Virol, 86, p5278-5287.
  • hsa-miR-6125 “hsa-mir-6125” (miRBase Accession No. MI0021259, SEQ ID NO: 223) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6756-5p gene or “hsa-miR-6756-5p” refers to the hsa-miR-6756-5p gene described in SEQ ID NO: 29 (miRBase Accession No. MIMAT0027412) and other species homologs or orthologs.
  • the hsa-miR-6756-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6756-5p” is known as “hsa-mir-6756” (miRBase Accession No. MI0022601, SEQ ID NO: 224) having a hairpin-like structure as a precursor.
  • hsa-miR-1228-3p gene or “hsa-miR-1228-3p” refers to the hsa-miR-1228-3p gene described in SEQ ID NO: 30 (miRBase Accession No. MIMAT0005583) and other species homologs or orthologs.
  • the hsa-miR-1228-3p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336.
  • “hsa-miR-1228-3p” is known as “hsa-mir-1228” (miRBase Accession No. MI0006318, SEQ ID NO: 225) having a hairpin-like structure as a precursor.
  • hsa-miR-8063 gene or “hsa-miR-8063” refers to the hsa-miR-8063 gene (miRBase Accession No. MIMAT0030990) described in SEQ ID NO: 31 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-8063 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, Vol. 39, p480-487.
  • hsa-miR-8063 “hsa-mir-8063” (miRBase Accession No. MI0025899, SEQ ID NO: 226) having a hairpin-like structure as a precursor is known.
  • hsa-miR-8069 gene or “hsa-miR-8069” refers to the hsa-miR-8069 gene (miRBase Accession No. MIMAT0030996) described in SEQ ID NO: 32 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-8069 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, 39, p480-487.
  • hsa-miR-8069 “hsa-mir-8069” (miRBase Accession No. MI0025905, SEQ ID NO: 227) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6875-5p gene or “hsa-miR-6875-5p” refers to the hsa-miR-6875-5p gene described in SEQ ID NO: 33 (miRBase Accession No. MIMAT0027650) and other species homologs or orthologs.
  • the hsa-miR-6875-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6875-5p “hsa-mir-6875” (miRBase Accession No. MI0022722, SEQ ID NO: 228) having a hairpin-like structure as a precursor is known.
  • hsa-miR-3185 gene or “hsa-miR-3185” refers to the hsa-miR-3185 gene (miRBase Accession No. MIMAT0015065) described in SEQ ID NO: 34 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-3185 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685.
  • hsa-miR-3185 “hsa-mir-3185” (miRBase Accession No. MI0014227, SEQ ID NO: 229) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4433b-3p gene or “hsa-miR-4433b-3p” refers to the hsa-miR-4433b-3p gene described in SEQ ID NO: 35 (miRBase Accession No. MIMAT0030414) and other species homologs or orthologs.
  • the hsa-miR-4433b-3p gene can be obtained by the method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746.
  • hsa-mir-4433b “miRBase Accession No. MI0025511, SEQ ID NO: 230) having a hairpin-like structure as a precursor is known.
  • hsa-miR-687-5p gene or “hsa-miR-6887-5p” refers to the hsa-miR-6687-5p gene described in SEQ ID NO: 36 (miRBase Accession No. MIMAT0027674) and other species homologs or orthologs.
  • the hsa-miR-6687-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-687-5p” is known as “hsa-mir-6687” (miRBase Accession No. MI0022734, SEQ ID NO: 231) having a hairpin-like structure as a precursor.
  • hsa-miR-128-1-5p gene or “hsa-miR-128-1-5p” refers to the hsa-miR-128-1-5p set forth in SEQ ID NO: 37. Including genes (miRBBase Accession No. MIMAT0026477) and other species homologs or orthologs The hsa-miR-128-1-5p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p735-739.
  • “hsa-miR-128-1-5p” is known as “hsa-mir-128-1” (miRBase Accession No. MI0000447, SEQ ID NO: 232) having a hairpin-like structure as a precursor.
  • hsa-miR-6724-5p gene or “hsa-miR-6724-5p” refers to the hsa-miR-6724-5p gene described in SEQ ID NO: 38 (miRBase Accession No. MIMAT0025856) and other species homologs or orthologs.
  • the hsa-miR-6724-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, 497, p330-335.
  • “hsa-miR-6724-5p” “hsa-mir-6724” (miRBase Accession No. MI0022559, SEQ ID NO: 233) having a hairpin-like structure as a precursor is known.
  • hsa-miR-1914-3p gene or “hsa-miR-1914-3p” refers to the hsa-miR-1914-3p gene described in SEQ ID NO: 39 (miRBase Accession No. MIMAT0007890) and other species homologs or orthologs.
  • the hsa-miR-1914-3p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, Vol. 26, p2496-2505.
  • “hsa-miR-1914-3p” is known as “hsa-mir-1914” (miRBase Accession No. MI0008335, SEQ ID NO: 234) having a hairpin-like structure as a precursor.
  • hsa-miR-1225-5p gene or “hsa-miR-1225-5p” refers to the hsa-miR-1225-5p gene described in SEQ ID NO: 40 (miRBase Accession No. MIMAT0005572) and other species homologs or orthologs.
  • the hsa-miR-1225-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336.
  • “hsa-miR-1225-5p” is known as “hsa-mir-1225” (miRBase Accession No. MI0006311, SEQ ID NO: 235) having a hairpin-like structure as a precursor.
  • hsa-miR-4419b gene or “hsa-miR-4419b” refers to the hsa-miR-4419b gene (miRBase Accession No. MIMAT0019034) described in SEQ ID NO: 41 and other species. Includes homologs or orthologs.
  • the hsa-miR-4419b gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • hsa-miR-4419b “hsa-mir-4419b” (miRBase Accession No. MI0016861, SEQ ID NO: 236) having a hairpin-like structure as a precursor is known.
  • hsa-miR-7110-5p gene or “hsa-miR-7110-5p” refers to the hsa-miR-7110-5p gene described in SEQ ID NO: 42 (miRBase Accession No. MIMAT0028117) and other species homologs or orthologs.
  • the hsa-miR-7110-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-7110-5p “hsa-mir-7110” (miRBase Accession No. MI0022961, SEQ ID NO: 237) having a hairpin-like structure as a precursor is known.
  • hsa-miR-187-5p gene or “hsa-miR-187-5p” refers to the hsa-miR-187-5p gene described in SEQ ID NO: 43 (miRBase Accession No. MIMAT0004561) and other species homologs or orthologs.
  • the hsa-miR-187-5p gene can be obtained by the method described in Lim LP et al., 2003, Science, 299, p1540.
  • “hsa-miR-187-5p” is known as “hsa-mir-187” (miRBase Accession No. MI000000274, SEQ ID NO: 238) having a hairpin-like structure as a precursor.
  • hsa-miR-3184-5p gene or “hsa-miR-3184-5p” refers to the hsa-miR-3184-5p gene described in SEQ ID NO: 44 (miRBase Accession No. MIMAT0015064) and other species homologs or orthologs.
  • the hsa-miR-3184-5p gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685.
  • “hsa-miR-3184-5p” “hsa-mir-3184” (miRBase Accession No. MI0014226, SEQ ID NO: 239) having a hairpin-like structure as a precursor is known.
  • hsa-miR-204-3p gene or “hsa-miR-204-3p” refers to the hsa-miR-204-3p gene described in SEQ ID NO: 45 (miRBase Accession No. MIMAT0022693) and other species homologs or orthologs.
  • the hsa-miR-204-3p gene can be obtained by the method described in Lim LP et al., 2003, Science, 299, p1540.
  • “hsa-miR-204-3p” is known as “hsa-mir-204” (miRBase Accession No. MI00000028, SEQ ID NO: 240) having a hairpin-like structure as a precursor.
  • hsa-miR-5572 gene or “hsa-miR-5572” refers to the hsa-miR-5572 gene (miRBase Accession No. MIMAT0022260) described in SEQ ID NO: 46 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-5572 gene can be obtained by the method described in Tandon M, et al., 2012, Oral Dis, 18, p127-131.
  • hsa-miR-5572 “hsa-mir-5572” (miRBase Accession No. MI0019117, SEQ ID NO: 241) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6729-5p gene or “hsa-miR-6729-5p” refers to the hsa-miR-6729-5p gene described in SEQ ID NO: 47 (miRBase Accession No. MIMAT0027359) and other species homologs or orthologs.
  • the hsa-miR-6729-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6729-5p “hsa-mir-6729” (miRBase Accession No. MI0022574, SEQ ID NO: 242) having a hairpin-like structure as a precursor is known.
  • hsa-miR-615-5p gene or “hsa-miR-615-5p” refers to the hsa-miR-615-5p gene described in SEQ ID NO: 48 (miRBase Accession No. MIMAT0004804) and other species homologs or orthologs.
  • the hsa-miR-615-5p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, 103, p3687-3692.
  • “Hsa-miR-615-5p” is known as “hsa-mir-615” (miRBase Accession No. MI0003628, SEQ ID NO: 243) having a hairpin-like structure as a precursor.
  • hsa-miR-6749-5p gene or “hsa-miR-6749-5p” refers to the hsa-miR-6749-5p gene described in SEQ ID NO: 49 (miRBase Accession No. MIMAT0027398) and other species homologs or orthologs.
  • the hsa-miR-6749-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6749-5p” is known as “hsa-mir-6749” (miRBase Accession No. MI0022594, SEQ ID NO: 244) having a hairpin-like structure as a precursor.
  • hsa-miR-6515-3p gene or “hsa-miR-6515-3p” refers to the hsa-miR-6515-3p gene described in SEQ ID NO: 50 (miRBase Accession No. MIMAT0025487) and other species homologs or orthologs.
  • the hsa-miR-6515-3p gene can be obtained by the method described in Joyce CE et al., 2011, Hum Mol Genet, 20, p4025-4040.
  • “hsa-miR-6515-3p” is known as “hsa-mir-6515” (miRBase Accession No. MI0022227, SEQ ID NO: 245) having a hairpin-like structure as a precursor.
  • hsa-miR-3937 gene or “hsa-miR-3937” refers to the hsa-miR-3937 gene (miRBase Accession No. MIMAT0018352) described in SEQ ID NO: 51 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-3937 gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, 5, e10563.
  • hsa-miR-3937 “hsa-mir-3937” (miRBase Accession No. MI0016593, SEQ ID NO: 246) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6840-3p gene or “hsa-miR-6840-3p” refers to the hsa-miR-6840-3p gene described in SEQ ID NO: 52 (miRBase Accession No. MIMAT0027583) and other species homologs or orthologs.
  • the hsa-miR-6840-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6840-3p” is known as “hsa-mir-6840” (miRBase Accession No. MI0022686, SEQ ID NO: 247) having a hairpin-like structure as a precursor.
  • hsa-miR-6893-5p gene or “hsa-miR-6893-5p” refers to the hsa-miR-6893-5p gene described in SEQ ID NO: 53 (miRBase Accession No. MIMAT0027686) and other species homologs or orthologs.
  • the hsa-miR-6893-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6893-5p” is known as “hsa-mir-6893” (miRBase Accession No. MI0022740, SEQ ID NO: 248) having a hairpin-like structure as a precursor.
  • hsa-miR-4728-5p gene or “hsa-miR-4728-5p” refers to the hsa-miR-4728-5p gene described in SEQ ID NO: 54 (miRBase Accession No. MIMAT0019849) and other species homologs or orthologs.
  • the hsa-miR-4728-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4728-5p” is known as “hsa-mir-4728” (miRBase Accession No. MI0017365, SEQ ID NO: 249) having a hairpin-like structure as a precursor.
  • hsa-miR-6717-5p gene or “hsa-miR-6717-5p” refers to the hsa-miR-6717-5p gene described in SEQ ID NO: 55 (miRBase Accession No. MIMAT0025846) and other species homologs or orthologs.
  • the hsa-miR-6717-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, 497, p330-335.
  • hsa-miR-6717-5p “hsa-mir-6717” (miRBase Accession No. MI0022551, SEQ ID NO: 250) having a hairpin-like structure as a precursor is known.
  • hsa-miR-7113-3p gene or “hsa-miR-7113-3p” refers to the hsa-miR-7113-3p gene described in SEQ ID NO: 56 (miRBase Accession No. MIMAT0028124) and other species homologs or orthologs.
  • the hsa-miR-7113-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-7113-3p” is known as “hsa-mir-7113” (miRBase Accession No. MI0022964, SEQ ID NO: 251) having a hairpin-like structure as a precursor.
  • hsa-miR-4665-5p gene or “hsa-miR-4665-5p” refers to the hsa-miR-4665-5p gene described in SEQ ID NO: 57 (miRBase Accession No. MIMAT0019739) and other species homologs or orthologs.
  • the hsa-miR-4665-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4665-5p” “hsa-mir-4665” (miRBase Accession No. MI0017295, SEQ ID NO: 220) having a hairpin-like structure as a precursor is known.
  • hsa-miR-642b-3p gene or “hsa-miR-642b-3p” refers to the hsa-miR-642b-3p gene described in SEQ ID NO: 58 (miRBase Accession No. MIMAT0018444) and other species homologs or orthologs.
  • the hsa-miR-642b-3p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, Vol. 8, p58.
  • “hsa-miR-642b-3p” is known as “hsa-mir-642b” (miRBase Accession No. MI0016685, SEQ ID NO: 252) having a hairpin-like structure as a precursor.
  • hsa-miR-7109-5p gene or “hsa-miR-7109-5p” refers to the hsa-miR-7109-5p gene described in SEQ ID NO: 59 (miRBase Accession No. MIMAT0028115) and other species homologs or orthologs.
  • the hsa-miR-7109-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-7109-5p “hsa-mir-7109” (miRBase Accession No. MI0022960, SEQ ID NO: 253) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6842-5p gene or “hsa-miR-6842-5p” refers to the hsa-miR-6842-5p gene described in SEQ ID NO: 60 (miRBase Accession No. MIMAT0027586) and other species homologs or orthologs.
  • the hsa-miR-6842-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6842-5p” is known as “hsa-mir-6842” (miRBase Accession No. MI0022688, SEQ ID NO: 254) having a hairpin-like structure as a precursor.
  • hsa-miR-4442 gene or “hsa-miR-4442” refers to the hsa-miR-4442 gene (miRBase Accession No. MIMAT0018960) described in SEQ ID NO: 61 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4442 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • hsa-mir-4442 (miRBase Accession No. MI0016785, SEQ ID NO: 255) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4433-3p gene or “hsa-miR-4433-3p” refers to the hsa-miR-4433-3p gene described in SEQ ID NO: 62 (miRBase Accession No. MIMAT0018949) and other species homologs or orthologs.
  • the hsa-miR-4433-3p gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • “hsa-miR-4433-3p” is known as “hsa-mir-4433” (miRBase Accession No. MI0016773, SEQ ID NO: 256) having a hairpin-like structure as a precursor.
  • hsa-miR-4707-5p gene or “hsa-miR-4707-5p” refers to the hsa-miR-4707-5p gene described in SEQ ID NO: 63 (miRBase Accession No. MIMAT0019807) and other species homologs or orthologs.
  • the hsa-miR-4707-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • hsa-miR-4707-5p “hsa-mir-4707” (miRBase Accession No. MI0017340, SEQ ID NO: 257) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6126 gene or “hsa-miR-6126” refers to the hsa-miR-6126 gene (miRBase Accession No. MIMAT0024599) described in SEQ ID NO: 64 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-6126 gene can be obtained by the method described in Smith JL et al., 2012, J Virol, 86, p5278-5287.
  • “Hsa-miR-6126” is known as “hsa-mir-6126” (miRBase Accession No. MI0021260, SEQ ID NO: 258) having a hairpin-like structure as a precursor.
  • hsa-miR-4449 gene or “hsa-miR-4449” refers to the hsa-miR-4449 gene (miRBase Accession No. MIMAT0018968) described in SEQ ID NO: 65 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-4449 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • hsa-mir-4449 (miRBase Accession No. MI0016792, SEQ ID NO: 259) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4706 gene or “hsa-miR-4706” refers to the hsa-miR-4706 gene (miRBase Accession No. MIMAT0019806) described in SEQ ID NO: 66 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4706 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • hsa-miR-4706 “hsa-mir-4706” (miRBase Accession No. MI0017339, SEQ ID NO: 260) having a hairpin-like structure as a precursor is known.
  • hsa-miR-1913 gene or “hsa-miR-1913” refers to the hsa-miR-1913 gene (miRBase Accession No. MIMAT0007888) described in SEQ ID NO: 67 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-1913 gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, 26, p2496-2505.
  • “hsa-miR-1913” is known as “hsa-mir-1913” (miRBase Accession No. MI0008334, SEQ ID NO: 261) having a hairpin-like structure as a precursor.
  • hsa-miR-602 gene or “hsa-miR-602” refers to the hsa-miR-602 gene (miRBase Accession No. MIMAT0003270) described in SEQ ID NO: 68 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-602 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, 103, p3687-3692.
  • “Hsa-miR-602” is known as “hsa-mir-602” (miRBase Accession No. MI0003615, SEQ ID NO: 262) having a hairpin-like structure as a precursor.
  • hsa-miR-939-5p gene or “hsa-miR-939-5p” refers to the hsa-miR-939-5p gene described in SEQ ID NO: 69 (miRBase Accession No. MIMAT0004982) and other species homologs or orthologs.
  • the hsa-miR-939-5p gene can be obtained by the method described in Lui WO et al., 2007, Cancer Res, Vol. 67, p6031-6043.
  • “hsa-miR-939-5p” is known as “hsa-mir-939” (miRBase Accession No. MI0005761, SEQ ID NO: 263) having a hairpin-like structure as a precursor.
  • hsa-miR-4695-5p gene or “hsa-miR-4695-5p” refers to the hsa-miR-4695-5p gene described in SEQ ID NO: 70 (miRBase Accession No. MIMAT0019788) and other species homologs or orthologs.
  • the hsa-miR-4695-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “Hsa-miR-4695-5p” is known as “hsa-mir-4695” (miRBase Accession No. MI0017328, SEQ ID NO: 264) having a hairpin-like structure as a precursor.
  • hsa-miR-711 gene or “hsa-miR-711” refers to the hsa-miR-711 gene (miRBase Accession No. MIMAT0012734) described in SEQ ID NO: 71 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-711 gene can be obtained by the method described in Artzi S et al., 2008, BMC Bioinformatics, Vol. 9, p39.
  • hsa-miR-711 “hsa-mir-711” (miRBase Accession No. MI0012488, SEQ ID NO: 265) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6816-5p gene or “hsa-miR-6816-5p” refers to the hsa-miR-6816-5p gene described in SEQ ID NO: 72 (miRBase Accession No. MIMAT0027532) and other species homologs or orthologs.
  • the hsa-miR-6816-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6816-5p” is known as “hsa-mir-6816” (miRBase Accession No. MI0022661, SEQ ID NO: 266) having a hairpin-like structure as a precursor.
  • hsa-miR-4632-5p gene or “hsa-miR-4632-5p” refers to the hsa-miR-4632-5p gene described in SEQ ID NO: 73 (miRBase Accession No. MIMAT0022977) and other species homologs or orthologs.
  • the hsa-miR-4632-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “Hsa-miR-4632-5p” is known as “hsa-mir-4632” (miRBase Accession No. MI0017259, SEQ ID NO: 267) having a hairpin-like structure as a precursor.
  • hsa-miR-6721-5p gene or “hsa-miR-6721-5p” refers to the hsa-miR-6721-5p gene described in SEQ ID NO: 74 (miRBase Accession No. MIMAT0025852) and other species homologs or orthologs.
  • the hsa-miR-6721-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, 497, p330-335.
  • “hsa-miR-6721-5p” is known as “hsa-mir-6721” (miRBase Accession No. MI0022556, SEQ ID NO: 268) having a hairpin-like structure as a precursor.
  • hsa-miR-7847-3p gene or “hsa-miR-7847-3p” refers to the hsa-miR-7847-3p gene described in SEQ ID NO: 75 (miRBase Accession No. MIMAT0030422) and other species homologs or orthologs.
  • the hsa-miR-7847-3p gene can be obtained by the method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746.
  • hsa-miR-7847-3p “hsa-mir-7847” (miRBase Accession No. MI0025517, SEQ ID NO: 269) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6132 gene or “hsa-miR-6132” refers to the hsa-miR-6132 gene (miRBase Accession No. MIMAT0024616) described in SEQ ID NO: 76 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-6132 gene can be obtained by the method described in Dannemann M et al., 2012, Genome Biol Evol, Vol. 4, p552-564.
  • “hsa-miR-6132” is known as “hsa-mir-6132” (miRBase Accession No. MI0021277, SEQ ID NO: 270) having a hairpin-like structure as a precursor.
  • hsa-miR-887-3p gene or “hsa-miR-887-3p” refers to the hsa-miR-887-3p gene described in SEQ ID NO: 77 (miRBase Accession No. MIMAT0004951) and other species homologs or orthologs.
  • the hsa-miR-887-3p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, 16: p1299-1298.
  • hsa-miR-887-3p “hsa-mir-887” (miRBase Accession No. MI0005562, SEQ ID NO: 271) having a hairpin-like structure as a precursor is known.
  • hsa-miR-3679-3p gene or “hsa-miR-3679-3p” refers to the hsa-miR-3679-3p gene described in SEQ ID NO: 78 (miRBase Accession No. MIMAT0018105) and other species homologs or orthologs.
  • the hsa-miR-3679-3p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, 5, e9637.
  • “Hsa-miR-3679-3p” is known as “hsa-mir-3679” (miRBase Accession No. MI0016080, SEQ ID NO: 205) having a hairpin-like structure as a precursor.
  • hsa-miR-6784-5p gene or “hsa-miR-6784-5p” refers to the hsa-miR-6784-5p gene described in SEQ ID NO: 79 (miRBase Accession No. MIMAT0027468) and other species homologs or orthologs.
  • the hsa-miR-6784-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6784-5p “hsa-mir-6784” (miRBase Accession No. MI0022629, SEQ ID NO: 272) having a hairpin-like structure as a precursor is known.
  • hsa-miR-1249 gene or “hsa-miR-1249” refers to the hsa-miR-1249 gene (miRBase Accession No. MIMAT0005901) described in SEQ ID NO: 80 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-1249 gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, 18, p610-621.
  • “hsa-miR-1249” is known as “hsa-mir-1249” (miRBase Accession No. MI0006384, SEQ ID NO: 273) having a hairpin-like structure as a precursor.
  • hsa-miR-937-5p gene or “hsa-miR-937-5p” refers to the hsa-miR-937-5p gene described in SEQ ID NO: 81 (miRBase Accession No. MIMAT0022938) and other species homologs or orthologs.
  • the hsa-miR-937-5p gene can be obtained by the method described in Lui WO et al., 2007, Cancer Res, Vol. 67, p6031-6043.
  • hsa-miR-937-5p “hsa-mir-937” (miRBase Accession No. MI0005759, SEQ ID NO: 274) having a hairpin-like structure as a precursor is known.
  • hsa-miR-5195-3p gene or “hsa-miR-5195-3p” refers to the hsa-miR-5195-3p gene described in SEQ ID NO: 82 (miRBase Accession No. MIMAT0021127) and other species homologs or orthologs.
  • the hsa-miR-5195-3p gene can be obtained by the method described in Schotte D et al., 2011, Leukemia, 25, p1389-1399.
  • “hsa-miR-5195-3p” is known as “hsa-mir-5195” (miRBase Accession No. MI0018174, SEQ ID NO: 275) having a hairpin-like structure as a precursor.
  • hsa-miR-6732-5p gene or “hsa-miR-6732-5p” refers to the hsa-miR-6732-5p gene described in SEQ ID NO: 83 (miRBase Accession No. MIMAT0027365) and other species homologs or orthologs.
  • the hsa-miR-6732-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6732-5p “hsa-mir-6732” (miRBase Accession No. MI0022577, SEQ ID NO: 276) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4417 gene or “hsa-miR-4417” refers to the hsa-miR-4417 gene (miRBase Accession No. MIMAT0018929) described in SEQ ID NO: 84 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4417 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • hsa-miR-4417 is known as “hsa-mir-4417” (miRBase Accession No. MI0016753, SEQ ID NO: 277), which has a hairpin-like structure as a precursor.
  • hsa-miR-4281 gene or “hsa-miR-4281” refers to the hsa-miR-4281 gene (miRBase Accession No. MIMAT0016907) described in SEQ ID NO: 85 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4281 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192.
  • hsa-miR-4281 “hsa-mir-4281” (miRBase Accession No. MI0015885, SEQ ID NO: 278) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4734 gene or “hsa-miR-4734” refers to the hsa-miR-4734 gene (miRBase Accession No. MIMAT0019859) described in SEQ ID NO: 86 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4734 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4734” is known as “hsa-mir-4734” (miRBase Accession No. MI0017371, SEQ ID NO: 279) having a hairpin-like structure as a precursor.
  • hsa-miR-6766-3p gene or “hsa-miR-6766-3p” refers to the hsa-miR-6766-3p gene described in SEQ ID NO: 87 (miRBase Accession No. MIMAT0027433) and other species homologs or orthologs.
  • the hsa-miR-6766-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6766-3p “hsa-mir-6766” (miRBase Accession No. MI0022611, SEQ ID NO: 280) having a hairpin-like structure as a precursor is known.
  • hsa-miR-663a gene or “hsa-miR-663a” refers to the hsa-miR-663a gene (miRBase Accession No. MIMAT0003326) described in SEQ ID NO: 88 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-663a gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, p3687-3692.
  • “hsa-miR-663a” is known as “hsa-mir-663a” (miRBase Accession No. MI0003672, SEQ ID NO: 281) having a hairpin-like structure as a precursor.
  • hsa-miR-4513 gene or “hsa-miR-4513” refers to the hsa-miR-4513 gene (miRBase Accession No. MIMAT0019050) described in SEQ ID NO: 89 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4513 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • hsa-mir-4513 (miRBase Accession No. MI0016879, SEQ ID NO: 282) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6781-5p gene or “hsa-miR-6781-5p” refers to the hsa-miR-6781-5p gene described in SEQ ID NO: 90 (miRBase Accession No. MIMAT0027462) and other species homologs or orthologs.
  • the hsa-miR-6781-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6781-5p” is known as “hsa-mir-6781” (miRBase Accession No. MI0022626, SEQ ID NO: 283) having a hairpin-like structure as a precursor.
  • hsa-miR-1227-5p gene or “hsa-miR-1227-5p” refers to the hsa-miR-1227-5p gene described in SEQ ID NO: 91 (miRBase Accession No. MIMAT0022941) and other species homologs or orthologs.
  • the hsa-miR-1227-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336.
  • “Hsa-miR-1227-5p” is known as “hsa-mir-1227” (miRBase Accession No. MI0006316, SEQ ID NO: 284) having a hairpin-like structure as a precursor.
  • hsa-miR-6845-5p gene or “hsa-miR-6845-5p” refers to the hsa-miR-6845-5p gene described in SEQ ID NO: 92 (miRBase Accession No. MIMAT0027590) and other species homologs or orthologs.
  • the hsa-miR-6845-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6845-5p” is known as “hsa-mir-6845” (miRBase Accession No. MI0022691, SEQ ID NO: 285) having a hairpin-like structure as a precursor.
  • hsa-miR-6798-5p gene or “hsa-miR-6798-5p” refers to the hsa-miR-6798-5p gene described in SEQ ID NO: 93 (miRBase Accession No. MIMAT0027496) and other species homologs or orthologs.
  • the hsa-miR-6798-5p gene can be obtained by the method described in Ladwig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6798-5p” is known as “hsa-mir-6798” (miRBase Accession No. MI0022643, SEQ ID NO: 286) having a hairpin-like structure as a precursor.
  • hsa-miR-3620-5p gene or “hsa-miR-3620-5p” refers to the hsa-miR-3620-5p gene described in SEQ ID NO: 94 (miRBase Accession No. MIMAT0022967) and other species homologs or orthologs.
  • the hsa-miR-3620-5p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, Vol. 8, p58.
  • “hsa-miR-3620-5p” is known as “hsa-mir-3620” (miRBase Accession No. MI0016011, SEQ ID NO: 287) having a hairpin-like structure as a precursor.
  • hsa-miR-1915-5p gene or “hsa-miR-1915-5p” refers to the hsa-miR-1915-5p gene (miRBase Accession No. MIMAT0007891) and other species homologs or orthologs.
  • the hsa-miR-1915-5p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, Vol. 26, p2496-2505.
  • “hsa-miR-1915-5p” is known as “hsa-mir-1915” (miRBase Accession No. MI0008336, SEQ ID NO: 288) having a hairpin-like structure as a precursor.
  • hsa-miR-4294 gene or “hsa-miR-4294” refers to the hsa-miR-4294 gene (miRBase Accession No. MIMAT0016849) described in SEQ ID NO: 96 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-4294 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192.
  • hsa-miR-4294 “hsa-mir-4294” (miRBase Accession No. MI0015827, SEQ ID NO: 289) having a hairpin-like structure as a precursor is known.
  • hsa-miR-642a-3p gene or “hsa-miR-642a-3p” refers to the hsa-miR-642a-3p gene described in SEQ ID NO: 97 (miRBase Accession No. MIMAT0020924) and other species homologs or orthologs.
  • the hsa-miR-642a-3p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, 103, p3687-3692.
  • “hsa-miR-642a-3p” is known as “hsa-mir-642a” (miRBase Accession No. MI0003657, SEQ ID NO: 290) having a hairpin-like structure as a precursor.
  • hsa-miR-371a-5p gene or “hsa-miR-371a-5p” refers to the hsa-miR-371a-5p gene described in SEQ ID NO: 98 (miRBase Accession No. MIMAT0004687) and other species homologs or orthologs.
  • the hsa-miR-371a-5p gene can be obtained by the method described in Suh MR et al., 2004, Dev Biol, 270, p488-498.
  • hsa-miR-371a-5p “hsa-mir-371a” (miRBase Accession No. MI000079, SEQ ID NO: 291) having a hairpin-like structure as a precursor is known.
  • hsa-miR-940 gene or “hsa-miR-940” refers to the hsa-miR-940 gene (miRBase Accession No. MIMAT0004983) described in SEQ ID NO: 99 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-940 gene can be obtained by the method described in Lui WO et al., 2007, Cancer Res, Vol. 67, p6031-43.
  • hsa-miR-940 “hsa-mir-940” (miRBase Accession No. MI0005762, SEQ ID NO: 292) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4450 gene or “hsa-miR-4450” refers to the hsa-miR-4450 gene (miRBase Accession No. MIMAT0018971) described in SEQ ID NO: 100 or other species. Includes homologs or orthologs.
  • the hsa-miR-4450 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • hsa-miR-4450 is known as “hsa-mir-4450” (miRBase Accession No. MI0016795, SEQ ID NO: 293) having a hairpin-like structure as a precursor.
  • hsa-miR-4723-5p gene or “hsa-miR-4723-5p” refers to the hsa-miR-4723-5p gene described in SEQ ID NO: 101 (miRBase Accession No. MIMAT0019838) and other species homologs or orthologs.
  • the hsa-miR-4723-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4723-5p” “hsa-mir-4723” (miRBase Accession No. MI0017359, SEQ ID NO: 294) having a hairpin-like structure as a precursor is known.
  • hsa-miR-1469 gene or “hsa-miR-1469” refers to the hsa-miR-1469 gene (miRBase Accession No. MIMAT0007347) described in SEQ ID NO: 102 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-1469 gene can be obtained by the method described in Kawaji H et al., 2008, BMC Genomics, Vol. 9, p157.
  • hsa-miR-1469 “hsa-mir-1469” (miRBase Accession No. MI00000074, SEQ ID NO: 295) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6861-5p gene or “hsa-miR-6861-5p” refers to the hsa-miR-6861-5p gene described in SEQ ID NO: 103 (miRBase Accession No. MIMAT0027623) and other species homologs or orthologs.
  • the hsa-miR-6861-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6861-5p “hsa-mir-6861” (miRBase Accession No. MI0022708, SEQ ID NO: 296) having a hairpin-like structure as a precursor is known.
  • hsa-miR-7975 gene or “hsa-miR-7975” refers to the hsa-miR-7975 gene (miRBase Accession No. MIMAT0031178) described in SEQ ID NO: 104 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-7975 gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, online version.
  • hsa-miR-7975 is known as “hsa-mir-7975” (miRBase Accession No. MI0025751, SEQ ID NO: 297), which has a hairpin-like structure as a precursor.
  • hsa-miR-6879-5p gene or “hsa-miR-6879-5p” refers to the hsa-miR-6879-5p gene described in SEQ ID NO: 105 (miRBase Accession No. MIMAT0027658) and other species homologs or orthologs.
  • the hsa-miR-6879-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6879-5p “hsa-mir-6879” (miRBase Accession No. MI0022726, SEQ ID NO: 298) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6802-5p gene or “hsa-miR-6802-5p” refers to the hsa-miR-6802-5p gene described in SEQ ID NO: 106 (miRBase Accession No. MIMAT0027504) and other species homologs or orthologs.
  • the hsa-miR-6802-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6802-5p” is known as “hsa-mir-6802” (miRBase Accession No. MI0022647, SEQ ID NO: 299) having a hairpin-like structure as a precursor.
  • hsa-miR-1268b gene or “hsa-miR-1268b” refers to the hsa-miR-1268b gene (miRBase Accession No. MIMAT0018925) described in SEQ ID NO: 107 and other species. Includes homologs or orthologs.
  • the hsa-miR-1268b gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • hsa-miR-1268b is known as “hsa-mir-1268b” (miRBase Accession No. MI0016748, SEQ ID NO: 300) having a hairpin-like structure as a precursor.
  • hsa-miR-663b gene or “hsa-miR-663b” refers to the hsa-miR-663b gene (miRBase Accession No. MIMAT0005867) described in SEQ ID NO: 108 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-663b gene can be obtained by the method described in Takada S et al., 2008, Leukemia, Vol. 22, p1274-1278.
  • hsa-miR-663b “hsa-mir-663b” (miRBase Accession No. MI0006336, SEQ ID NO: 301) having a hairpin-like structure as a precursor is known.
  • hsa-miR-125a-3p gene or “hsa-miR-125a-3p” refers to the hsa-miR-125a-3p gene described in SEQ ID NO: 109 (miRBase Accession No. MIMAT0004602) and other species homologs or orthologs.
  • the hsa-miR-125a-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p735-739.
  • “hsa-miR-125a-3p” “hsa-mir-125a” (miRBase Accession No. MI000069, SEQ ID NO: 302) having a hairpin-like structure as a precursor is known.
  • hsa-miR-2861 gene or “hsa-miR-2861” refers to the hsa-miR-2861 gene (miRBase Accession No. MIMAT0013802) described in SEQ ID NO: 110 and other species. Includes homologs or orthologs.
  • the hsa-miR-2861 gene can be obtained by the method described in Li H, et al., 2009, J Clin Invest, 119, p3666-3777.
  • “hsa-miR-2861” is known as “hsa-mir-2861” (miRBase Accession No. MI0013006, SEQ ID NO: 303), which has a hairpin-like structure as a precursor.
  • hsa-miR-6088 gene or “hsa-miR-6088” refers to the hsa-miR-6088 gene (miRBase Accession No. MIMAT0023713) described in SEQ ID NO: 111 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-6088 gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev, 21, p2049-2057.
  • hsa-miR-6088 “hsa-mir-6088” (miRBase Accession No. MI0020365, SEQ ID NO: 304) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4758-5p gene or “hsa-miR-4758-5p” refers to the hsa-miR-4758-5p gene (miRBase Accession No. MIMAT0019903) and other species homologs or orthologs.
  • the hsa-miR-4758-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4758-5p” is known as “hsa-mir-4758” (miRBase Accession No. MI0017399, SEQ ID NO: 305) having a hairpin-like structure as a precursor.
  • hsa-miR-296-3p gene or “hsa-miR-296-3p” refer to the hsa-miR-296-3p gene described in SEQ ID NO: 113 (miRBase Accession No. MIMAT0004679) and other species homologs or orthologs.
  • the hsa-miR-296-3p gene can be obtained by the method described in Houbavy HB et al., 2003, Dev Cell, Vol. 5, p351-358.
  • “hsa-miR-296-3p” is known as “hsa-mir-296” (miRBase Accession No. MI000047, SEQ ID NO: 306) having a hairpin-like structure as a precursor.
  • hsa-miR-6738-5p gene or “hsa-miR-6738-5p” refers to the hsa-miR-6738-5p gene described in SEQ ID NO: 114 (miRBase Accession No. MIMAT0027377) and other species homologs or orthologs.
  • the hsa-miR-6738-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6738-5p “hsa-mir-6738” (miRBase Accession No. MI0022583, SEQ ID NO: 307) having a hairpin-like structure as a precursor is known.
  • hsa-miR-671-5p gene or “hsa-miR-671-5p” refers to the hsa-miR-671-5p gene described in SEQ ID NO: 115 (miRBase Accession No. MIMAT0003880) and other species homologs or orthologs.
  • the hsa-miR-671-5p gene can be obtained by the method described in Berezikov E, et al., 2006, Genome Res, 16: p1299-1298.
  • “hsa-miR-671-5p” is known as “hsa-mir-671” (miRBase Accession No. MI0003760, SEQ ID NO: 308) having a hairpin-like structure as a precursor.
  • hsa-miR-4454 gene or “hsa-miR-4454” refers to the hsa-miR-4454 gene (miRBase Accession No. MIMAT0018976) described in SEQ ID NO: 116 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4454 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • hsa-mir-4454 (miRBase Accession No. MI0016800, SEQ ID NO: 309) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4516 gene or “hsa-miR-4516” refers to the hsa-miR-4516 gene (miRBase Accession No. MIMAT0019053) described in SEQ ID NO: 117 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4516 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • hsa-mir-4516 (miRBase Accession No. MI0016882, SEQ ID NO: 310) having a hairpin-like structure as a precursor is known.
  • hsa-miR-7845-5p gene or “hsa-miR-7845-5p” refers to the hsa-miR-7845-5p gene described in SEQ ID NO: 118 (miRBase Accession No. MIMAT0030420) and other species homologs or orthologs.
  • the hsa-miR-7845-5p gene can be obtained by the method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746.
  • hsa-miR-7845-5p “hsa-mir-7845” (miRBase Accession No. MI0025515, SEQ ID NO: 311) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4741 gene or “hsa-miR-4741” refers to the hsa-miR-4741 gene (miRBase Accession No. MIMAT0019871) described in SEQ ID NO: 119 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4741 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4741” is known as “hsa-mir-4741” (miRBase Accession No. MI0017379, SEQ ID NO: 312) having a hairpin-like structure as a precursor.
  • hsa-miR-92b-5p gene or “hsa-miR-92b-5p” refers to the hsa-miR-92b-5p gene described in SEQ ID NO: 120 (miRBase Accession No. MIMAT0004792) and other species homologs or orthologs.
  • the hsa-miR-92b-5p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, 103, p3687-3692.
  • “hsa-miR-92b-5p” is known as “hsa-mir-92b” (miRBase Accession No. MI0003560, SEQ ID NO: 313) having a hairpin-like structure as a precursor.
  • hsa-miR-6695-5p gene or “hsa-miR-6695-5p” refers to the hsa-miR-6695-5p gene described in SEQ ID NO: 121 (miRBase Accession No. MIMAT0027490) and other species homologs or orthologs.
  • the hsa-miR-6695-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6695-5p “hsa-mir-6695” (miRBase Accession No. MI0022640, SEQ ID NO: 314) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6805-3p gene or “hsa-miR-6805-3p” refers to the hsa-miR-6805-3p gene described in SEQ ID NO: 122 (miRBase Accession No. MIMAT0027511) and other species homologs or orthologs.
  • the hsa-miR-6805-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6805-3p” is known as “hsa-mir-6805” (miRBase Accession No. MI0022650, SEQ ID NO: 315) having a hairpin-like structure as a precursor.
  • hsa-miR-4725-3p gene or “hsa-miR-4725-3p” refers to the hsa-miR-4725-3p gene (miRBase Accession No. MIMAT0019844) and other species homologs or orthologs.
  • the hsa-miR-4725-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4725-3p” “hsa-mir-4725” (miRBase Accession No. MI0017362, SEQ ID NO: 316) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6782-5p gene or “hsa-miR-6782-5p” refers to the hsa-miR-6782-5p gene described in SEQ ID NO: 124 (miRBase Accession No. MIMAT0027464) and other species homologs or orthologs.
  • the hsa-miR-6782-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6782-5p” is known as “hsa-mir-6782” (miRBase Accession No. MI0022627, SEQ ID NO: 317) having a hairpin-like structure as a precursor.
  • hsa-miR-4688 gene or “hsa-miR-4688” refers to the hsa-miR-4688 gene (miRBase Accession No. MIMAT0019777) described in SEQ ID NO: 125 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-4688 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • hsa-miR-4688 “hsa-mir-4688” (miRBase Accession No. MI0017321, SEQ ID NO: 318) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6850-5p gene or “hsa-miR-6850-5p” refers to the hsa-miR-6850-5p gene described in SEQ ID NO: 126 (miRBase Accession No. MIMAT0027600) and other species homologs or orthologs.
  • the hsa-miR-6850-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-mir-6850 miRBase Accession No. MI0022696, SEQ ID NO: 319) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6777-5p gene or “hsa-miR-6777-5p” refers to the hsa-miR-6777-5p gene described in SEQ ID NO: 127 (miRBase Accession No. MIMAT0027454) and other species homologs or orthologs.
  • the hsa-miR-6777-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6777-5p “hsa-mir-6777” (miRBase Accession No. MI0022622, SEQ ID NO: 320) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6785-5p gene or “hsa-miR-6785-5p” refers to the hsa-miR-6785-5p gene described in SEQ ID NO: 128 (miRBase Accession No. MIMAT0027470) and other species homologs or orthologs.
  • the hsa-miR-6785-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6785-5p “hsa-mir-6785” (miRBase Accession No. MI0022630, SEQ ID NO: 321) having a hairpin-like structure as a precursor is known.
  • hsa-miR-7106-5p gene or “hsa-miR-7106-5p” refers to the hsa-miR-7106-5p gene described in SEQ ID NO: 129 (miRBase Accession No. MIMAT0028109) and other species homologs or orthologs.
  • the hsa-miR-7106-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-7106-5p “hsa-mir-7106” (miRBase Accession No. MI0022957, SEQ ID NO: 322) having a hairpin-like structure as a precursor is known.
  • hsa-miR-3663-3p gene or “hsa-miR-3663-3p” refer to the hsa-miR-3663-3p gene (miRBase Accession No. MIMAT0018085) and other species homologs or orthologs.
  • the hsa-miR-3663-3p gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, 5, e10563.
  • hsa-miR-3663-3p “hsa-mir-3663” (miRBase Accession No. MI0016064, SEQ ID NO: 323) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6131 gene or “hsa-miR-6131” refers to the hsa-miR-6131 gene (miRBase Accession No. MIMAT0024615) described in SEQ ID NO: 131 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-6131 gene can be obtained by the method described in Dannemann M et al., 2012, Genome Biol Evol, Vol. 4, p552-564.
  • “hsa-miR-6131” is known as “hsa-mir-6131” (miRBase Accession No. MI0021276, SEQ ID NO: 324) having a hairpin-like structure as a precursor.
  • hsa-miR-1915-3p gene or “hsa-miR-1915-3p” refers to the hsa-miR-1915-3p gene described in SEQ ID NO: 132 (miRBase Accession No. MIMAT0007892) and other species homologs or orthologs.
  • the hsa-miR-1915-3p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, Vol. 26, p2496-2505.
  • “hsa-miR-1915-3p” is known as “hsa-mir-1915” (miRBase Accession No. MI0008336, SEQ ID NO: 288) having a hairpin-like structure as a precursor.
  • hsa-miR-4532 gene or “hsa-miR-4532” refers to the hsa-miR-4532 gene (miRBase Accession No. MIMAT0019071) described in SEQ ID NO: 133 or other species. Includes homologs or orthologs.
  • the hsa-miR-4532 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • hsa-mir-4532 (miRBase Accession No. MI0016899, SEQ ID NO: 325) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6820-5p gene or “hsa-miR-6820-5p” refers to the hsa-miR-6820-5p gene described in SEQ ID NO: 134 (miRBase Accession No. MIMAT0027540) and other species homologs or orthologs.
  • the hsa-miR-6820-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6820-5p “hsa-mir-6820” (miRBase Accession No. MI0022665, SEQ ID NO: 326) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4689 gene or “hsa-miR-4687” refers to the hsa-miR-4689 gene (miRBase Accession No. MIMAT0019778) described in SEQ ID NO: 135 and other biological species. Includes homologs or orthologs.
  • the hsa-miR-4689 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4689” is known as “hsa-mir-4689” (miRBase Accession No. MI0017322, SEQ ID NO: 327) having a hairpin-like structure as a precursor.
  • hsa-miR-4638-5p gene or “hsa-miR-4638-5p” refers to the hsa-miR-4638-5p gene described in SEQ ID NO: 136 (miRBase Accession No. MIMAT0019695) and other species homologs or orthologs.
  • the hsa-miR-4638-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4638-5p” “hsa-mir-4638” (miRBase Accession No. MI0017265, SEQ ID NO: 328) having a hairpin-like structure as a precursor is known.
  • hsa-miR-3656 gene or “hsa-miR-3656” refers to the hsa-miR-3656 gene (miRBase Accession No. MIMAT0018076) described in SEQ ID NO: 137 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-3656 gene can be obtained by the method described in Meiri E et al., 2010, Nucleic Acids Res, 38, p6234-6246.
  • “hsa-miR-3656” is known as “hsa-mir-3656” (miRBase Accession No. MI0016056, SEQ ID NO: 329) having a hairpin-like structure as a precursor.
  • hsa-miR-3621 gene or “hsa-miR-3621” refers to the hsa-miR-3621 gene (miRBase Accession No. MIMAT0018002) described in SEQ ID NO: 138 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-3621 gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, Vol. 8, p58.
  • hsa-mir-3621 (miRBase Accession No. MI0016012, SEQ ID NO: 330) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6769b-5p gene or “hsa-miR-6769b-5p” refers to the hsa-miR-6769b-5p gene (miRBase Accession No. MIMAT0027620) and other species homologs or orthologs.
  • the hsa-miR-6769b-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6769b-5p” is known as “hsa-mir-6769b” (miRBase Accession No. MI0022706, SEQ ID NO: 331) having a hairpin-like structure as a precursor.
  • hsa-miR-149-3p gene or “hsa-miR-149-3p” refer to the hsa-miR-149-3p gene described in SEQ ID NO: 140 (miRBase Accession No. MIMAT0004609) and other species homologs or orthologs.
  • the hsa-miR-149-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p735-739.
  • “hsa-miR-149-3p” is known as “hsa-mir-149” (miRBase Accession No. MI0000478, SEQ ID NO: 332) having a hairpin-like structure as a precursor.
  • hsa-miR-23b-3p gene or “hsa-miR-23b-3p” refers to the hsa-miR-23b-3p gene described in SEQ ID NO: 141 (miRBase Accession No. MIMAT000018) and other species homologs or orthologs.
  • the hsa-miR-23b-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, 12, p735-739.
  • “hsa-miR-23b-3p” is known as “hsa-mir-23b” (miRBase Accession No. MI0000439, SEQ ID NO: 333) having a hairpin-like structure as a precursor.
  • hsa-miR-3135b gene or “hsa-miR-3135b” refers to the hsa-miR-3135b gene (miRBase Accession No. MIMAT0018985) described in SEQ ID NO: 142 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-3135b gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • “hsa-miR-3135b” is known as “hsa-mir-3135b” (miRBase Accession No. MI0016809, SEQ ID NO: 334) having a hairpin-like structure as a precursor.
  • hsa-miR-6848-5p gene or “hsa-miR-6848-5p” refers to the hsa-miR-6848-5p gene described in SEQ ID NO: 143 (miRBase Accession No. MIMAT0027596) and other species homologs or orthologs.
  • the hsa-miR-6848-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6848-5p” is known as “hsa-mir-6848” (miRBase Accession No. MI0022694, SEQ ID NO: 335) having a hairpin-like structure as a precursor.
  • hsa-miR-6769a-5p gene or “hsa-miR-6769a-5p” refers to the hsa-miR-6769a-5p gene described in SEQ ID NO: 144 (miRBase Accession No. MIMAT0027438) and other species homologs or orthologs.
  • the hsa-miR-6769a-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6769a-5p “hsa-mir-6769a” (miRBase Accession No. MI0022614, SEQ ID NO: 336) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4327 gene or “hsa-miR-4327” refers to the hsa-miR-4327 gene (miRBase Accession No. MIMAT0016889) described in SEQ ID NO: 145 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4327 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192.
  • “hsa-miR-4327” is known as “hsa-mir-4327” (miRBase Accession No. MI0015867, SEQ ID NO: 337) having a hairpin-like structure as a precursor.
  • hsa-miR-6765-3p gene or “hsa-miR-6765-3p” refers to the hsa-miR-6765-3p gene described in SEQ ID NO: 146 (miRBase Accession No. MIMAT0027431) and other species homologs or orthologs.
  • the hsa-miR-6765-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6765-3p “hsa-mir-6765” (miRBase Accession No. MI0022610, SEQ ID NO: 338) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6716-5p gene or “hsa-miR-6716-5p” refers to the hsa-miR-6716-5p gene described in SEQ ID NO: 147 (miRBase Accession No. MIMAT0025844) and other species homologs or orthologs.
  • the hsa-miR-6716-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, 497, p330-335.
  • “hsa-miR-6716-5p” is known as “hsa-mir-6716” (miRBase Accession No. MI0022550, SEQ ID NO: 339) having a hairpin-like structure as a precursor.
  • hsa-miR-6877-5p gene or “hsa-miR-6877-5p” refers to the hsa-miR-6877-5p gene described in SEQ ID NO: 148 (miRBase Accession No. MIMAT0027654) and other species homologs or orthologs.
  • the hsa-miR-6877-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “Hsa-miR-6877-5p” is known as “hsa-mir-6877” (miRBase Accession No. MI0022724, SEQ ID NO: 340) having a hairpin-like structure as a precursor.
  • hsa-miR-6727-5p gene or “hsa-miR-6727-5p” refers to the hsa-miR-6727-5p gene described in SEQ ID NO: 149 (miRBase Accession No. MIMAT0027355) and other species homologs or orthologs.
  • the hsa-miR-6727-5p gene can be obtained by the method described in Ladwig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6727-5p” is known as “hsa-mir-6727” (miRBase Accession No. MI0022572, SEQ ID NO: 341) having a hairpin-like structure as a precursor.
  • hsa-miR-4534 gene or “hsa-miR-4534” refers to the hsa-miR-4534 gene (miRBase Accession No. MIMAT0019073) described in SEQ ID NO: 150 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4534 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • “Hsa-miR-4534” is known as “hsa-mir-4534” (miRBase Accession No. MI0016901, SEQ ID NO: 342) having a hairpin-like structure as a precursor.
  • hsa-miR-614 gene or “hsa-miR-614” refers to the hsa-miR-614 gene (miRBase Accession No. MIMAT0003282) described in SEQ ID NO: 151 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-614 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci US A, 103, p3687-3692.
  • hsa-miR-614 “hsa-mir-614” (miRBase Accession No. MI0003627, SEQ ID NO: 343) having a hairpin-like structure as a precursor is known.
  • hsa-miR-1202 gene or “hsa-miR-1202” refers to the hsa-miR- 1202 gene (miRBase Accession No. MIMAT0005865) described in SEQ ID NO: 152 and other species. Includes homologs or orthologs.
  • the hsa-miR- 1202 gene can be obtained by the method described in Marton S, et al., 2008, Leukemia, Vol. 22, p330-338.
  • hsa-miR-1220 is known as “hsa-mir-1220” (miRBase Accession No. MI0006334, SEQ ID NO: 344) having a hairpin-like structure as a precursor.
  • hsa-miR-575 gene or “hsa-miR-575” refers to the hsa-miR-575 gene (miRBase Accession No. MIMAT0003240) described in SEQ ID NO: 153 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-575 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, p3687-3692.
  • hsa-miR-575 “hsa-mir-575” (miRBase Accession No. MI0003582, SEQ ID NO: 345) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6870-5p gene or “hsa-miR-6870-5p” refers to the hsa-miR-6870-5p gene described in SEQ ID NO: 154 (miRBase Accession No. MIMAT0027640) and other species homologs or orthologs.
  • the hsa-miR-6870-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6870-5p “hsa-mir-6870” (miRBase Accession No. MI0022717, SEQ ID NO: 346) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6722-3p gene or “hsa-miR-6722-3p” refers to the hsa-miR-6722-3p gene described in SEQ ID NO: 155 (miRBase Accession No. MIMAT0025854) and other species homologs or orthologs.
  • the hsa-miR-6722-3p gene can be obtained by the method described in Li Y et al., 2012, Gene, 497, p330-335.
  • hsa-miR-6722-3p “hsa-mir-6722” (miRBase Accession No. MI0022557, SEQ ID NO: 347) having a hairpin-like structure as a precursor is known.
  • hsa-miR-7777 gene or “hsa-miR-7777” refers to the hsa-miR-7777 gene (miRBase Accession No. MIMAT0031180) described in SEQ ID NO: 156 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-7777 gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, online version.
  • hsa-miR-7777 “hsa-mir-7777” (miRBase Accession No. MI0025753, SEQ ID NO: 348) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4649-5p gene or “hsa-miR-4649-5p” refers to the hsa-miR-4649-5p gene described in SEQ ID NO: 157 (miRBase Accession No. MIMAT0019711) and other species homologs or orthologs.
  • the hsa-miR-4649-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4649-5p” “hsa-mir-4649” (miRBase Accession No. MI0017276, SEQ ID NO: 349) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4675 gene or “hsa-miR-4675” refers to the hsa-miR-4675 gene (miRBase Accession No. MIMAT0019757) described in SEQ ID NO: 158 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4675 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4675” is known as “hsa-mir-4675” (miRBase Accession No. MI0017306, SEQ ID NO: 350) having a hairpin-like structure as a precursor.
  • hsa-miR-6075 gene or “hsa-miR-6075” refers to the hsa-miR-6075 gene (miRBase Accession No. MIMAT0023700) described in SEQ ID NO: 159 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-6075 gene can be obtained by the method described in Voellenkle C et al., 2012, RNA, 18, p472-484.
  • hsa-miR-6075 “hsa-mir-6075” (miRBase Accession No. MI0020352, SEQ ID NO: 351) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6679-5p gene or “hsa-miR-6679-5p” refers to the hsa-miR-6679-5p gene described in SEQ ID NO: 160 (miRBase Accession No. MIMAT0027458) and other species homologs or orthologs.
  • the hsa-miR-6679-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6779-5p” is known as “hsa-mir-6679” (miRBase Accession No. MI0022624, SEQ ID NO: 352) having a hairpin-like structure as a precursor.
  • hsa-miR-4271 gene or “hsa-miR-4271” refers to the hsa-miR-4271 gene (miRBase Accession No. MIMAT0016901) described in SEQ ID NO: 161 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4271 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192.
  • hsa-miR-4271 “hsa-mir-4271” (miRBase Accession No. MI0015879, SEQ ID NO: 353) having a hairpin-like structure as a precursor is known.
  • hsa-miR-3196 gene or “hsa-miR-3196” refers to the hsa-miR-3196 gene (miRBase Accession No. MIMAT0015080) described in SEQ ID NO: 162 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-3196 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685.
  • hsa-miR-3196 “hsa-mir-3196” (miRBase Accession No. MI0014241, SEQ ID NO: 354) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6803-5p gene or “hsa-miR-6803-5p” refers to the hsa-miR-6803-5p gene described in SEQ ID NO: 163 (miRBase Accession No. MIMAT0027506) and other species homologs or orthologs.
  • the hsa-miR-6803-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6803-5p” is known as “hsa-mir-6803” (miRBase Accession No. MI0022648, SEQ ID NO: 355) having a hairpin-like structure as a precursor.
  • hsa-miR-6789-5p gene or “hsa-miR-6789-5p” refers to the hsa-miR-6789-5p gene described in SEQ ID NO: 164 (miRBase Accession No. MIMAT0027478) and other species homologs or orthologs.
  • the hsa-miR-6789-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-miR-6789-5p “hsa-mir-6789” (miRBase Accession No. MI0022634, SEQ ID NO: 356) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4648 gene or “hsa-miR-4648” refers to the hsa-miR-4648 gene (miRBase Accession No. MIMAT0019710) described in SEQ ID NO: 165 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4648 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • hsa-miR-4648 “hsa-mir-4648” (miRBase Accession No. MI0017275, SEQ ID NO: 357) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4508 gene or “hsa-miR-4508” refers to the hsa-miR-4508 gene (miRBase Accession No. MIMAT0019045) described in SEQ ID NO: 166 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4508 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • hsa-mir-4508 (miRBase Accession No. MI0016872, SEQ ID NO: 358) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4749-5p gene or “hsa-miR-4749-5p” refers to the hsa-miR-4749-5p gene described in SEQ ID NO: 167 (miRBase Accession No. MIMAT0019885) and other species homologs or orthologs.
  • the hsa-miR-4749-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4749-5p” “hsa-mir-4749” (miRBase Accession No. MI0017388, SEQ ID NO: 359) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4505 gene or “hsa-miR-4505” refers to the hsa-miR-4505 gene (miRBase Accession No. MIMAT0019041) described in SEQ ID NO: 168 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4505 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • hsa-mir-4505 (miRBase Accession No. MI0016868, SEQ ID NO: 360) having a hairpin-like structure as a precursor is known.
  • hsa-miR-5698 gene or “hsa-miR-5698” refers to the hsa-miR-5698 gene (miRBase Accession No. MIMAT0022491) described in SEQ ID NO: 169 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-5698 gene can be obtained by the method described in Watahiki A et al., 2011, PLoS One, Vol. 6, e24950.
  • hsa-miR-5698 “hsa-mir-5698” (miRBase Accession No. MI0019305, SEQ ID NO: 361) having a hairpin-like structure as a precursor is known.
  • hsa-miR-1199-5p gene or “hsa-miR-1199-5p” refers to the hsa-miR-1199-5p gene described in SEQ ID NO: 170 (miRBase Accession No. MIMAT0031119) and other species homologs or orthologs.
  • the hsa-miR-1199-5p gene can be obtained by the method described in Salvi A et al., 2013, Int J Oncol, 42, p391-402.
  • “hsa-miR-1199-5p” is known as “hsa-mir-1199” (miRBase Accession No. MI0020340, SEQ ID NO: 362) having a hairpin-like structure as a precursor.
  • hsa-miR-4763-3p gene or “hsa-miR-4763-3p” refers to the hsa-miR-4763-3p gene described in SEQ ID NO: 171 (miRBase Accession No. MIMAT0019913) and other species homologs or orthologs.
  • the hsa-miR-4763-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4763-3p” is known as “hsa-mir-4763” (miRBase Accession No. MI0017404, SEQ ID NO: 363) having a hairpin-like structure as a precursor.
  • hsa-miR-1231 gene or “hsa-miR-1231” refers to the hsa-miR-1231 gene (miRBase Accession No. MIMAT0005586) described in SEQ ID NO: 172 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-1231 gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336.
  • “Hsa-miR-1231” is known as “hsa-mir-1231” (miRBase Accession No. MI0006321, SEQ ID NO: 364) having a hairpin-like structure as a precursor.
  • hsa-miR-1233-5p gene or “hsa-miR-1233-5p” refers to the hsa-miR-1233-5p gene (miRBase Accession No. 173 described in SEQ ID NO: 173). MIMAT0022943) and other species homologs or orthologs.
  • the hsa-miR-1233-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336.
  • “Hsa-miR-1233-5p” has a hairpin-like structure as a precursor thereof, “hsa-mir-1233-1, hsa-mir-12233-2” (miRBase Accession No. MI0006323, MI0015973, SEQ ID NO: 365, 366).
  • hsa-miR-150-3p gene or “hsa-miR-150-3p” refers to the hsa-miR-150-3p gene described in SEQ ID NO: 174 (miRBase Accession No. MIMAT0004610) and other species homologs or orthologs.
  • the hsa-miR-150-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p735-739.
  • “hsa-miR-150-3p” is known as “hsa-mir-150” (miRBase Accession No. MI0000479, SEQ ID NO: 367) having a hairpin-like structure as a precursor.
  • hsa-miR-1225-3p gene or “hsa-miR-1225-3p” refers to the hsa-miR-1225-3p gene described in SEQ ID NO: 175 (miRBase Accession No. MIMAT0005573) and other species homologs or orthologs.
  • the hsa-miR-1225-3p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336.
  • hsa-mir-1225 (miRBase Accession No. MI0006311, SEQ ID NO: 235) having a hairpin-like structure as a precursor is known.
  • hsa-miR-92a-2-5p gene or “hsa-miR-92a-2-5p” refers to the hsa-miR-92a-2-5p set forth in SEQ ID NO: 176. It includes genes (miRBase Accession No. MIMAT0004508) and other species homologues or orthologues.
  • the hsa-miR-92a-2-5p gene can be obtained by the method described in Murelatos Z et al., 2002, Genes Dev, 16, p720-728.
  • “hsa-miR-92a-2-5p” is known as “hsa-mir-92a-2” (miRBase Accession No. MI00000094, SEQ ID NO: 368) having a hairpin-like structure as a precursor.
  • hsa-miR-423-5p gene or “hsa-miR-423-5p” refers to the hsa-miR-423-5p gene described in SEQ ID NO: 177 (miRBase Accession No. MIMAT0004748) and other species homologs or orthologs.
  • the hsa-miR-423-5p gene can be obtained by the method described in Kasshima K et al., 2004, Biochem Biophys Res Commun, 322, p403-410.
  • “hsa-miR-423-5p” is known as “hsa-mir-423” (miRBase Accession No. MI0001445, SEQ ID NO: 369) having a hairpin-like structure as a precursor.
  • hsa-miR-1268a gene or “hsa-miR-1268a” refers to the hsa-miR-1268a gene (miRBase Accession No. MIMAT0005922) described in SEQ ID NO: 178 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-1268a gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, 18, p610-621.
  • “hsa-miR-1268a” is known as “hsa-mir-1268a” (miRBase Accession No. MI0006405, SEQ ID NO: 370) having a hairpin-like structure as a precursor.
  • hsa-miR-128-2-5p gene or “hsa-miR-128-2-5p” refers to the hsa-miR-128-2-5p described in SEQ ID NO: 179. It includes genes (miRBase Accession No. MIMAT0031095) and other species homologs or orthologs.
  • the hsa-miR-128-2-5p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p735-739.
  • “hsa-miR-128-2-5p” is known as “hsa-mir-128-2” (miRBase Accession No. MI000027, SEQ ID NO: 371) having a hairpin-like structure as a precursor.
  • hsa-miR-24-3p gene or “hsa-miR-24-3p” refers to the hsa-miR-24-3p gene described in SEQ ID NO: 180 (miRBase Accession No. MIMAT00000080) and other species homologues or orthologues.
  • the hsa-miR-24-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2001, Science, 294, p853-858.
  • “Hsa-miR-24-3p” has a hairpin-like structure as its precursor, “hsa-mir-24-1, hsa-mir-24-2” (miRBase Accession No. MI00000080, MI00000081, SEQ ID NO: 372, 373) are known.
  • hsa-miR-4697-5p gene or “hsa-miR-4697-5p” refers to the hsa-miR-4697-5p gene described in SEQ ID NO: 181 (miRBase Accession No. MIMAT0019791) and other species homologs or orthologs.
  • the hsa-miR-4697-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4697-5p” “hsa-mir-4697” (miRBase Accession No. MI0017330, SEQ ID NO: 374) having a hairpin-like structure as a precursor is known.
  • hsa-miR-3197 gene or “hsa-miR-3197” refers to the hsa-miR-3197 gene (miRBase Accession No. MIMAT0015082) described in SEQ ID NO: 182 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-3197 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685.
  • hsa-miR-3197 “hsa-mir-3197” (miRBase Accession No. MI0014245, SEQ ID NO: 375) having a hairpin-like structure as a precursor is known.
  • hsa-miR-675-5p gene or “hsa-miR-675-5p” refers to the hsa-miR-675-5p gene described in SEQ ID NO: 183 (miRBase Accession No. MIMAT0004284) and other species homologs or orthologs.
  • the hsa-miR-675-5p gene can be obtained by the method described in Cai X et al., 2007, RNA, Vol. 13, p313-316.
  • “Hsa-miR-675-5p” is known as “hsa-mir-675” (miRBase Accession No. MI0005416, SEQ ID NO: 376) having a hairpin-like structure as a precursor.
  • hsa-miR-4486 gene or “hsa-miR-4486” refers to the hsa-miR-4486 gene (miRBase Accession No. MIMAT0019020) described in SEQ ID NO: 184 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4486 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • hsa-miR-4486 is known as “hsa-mir-4486” (miRBase Accession No. MI0016847, SEQ ID NO: 377), which has a hairpin-like structure as a precursor.
  • hsa-miR-7107-5p gene or “hsa-miR-7107-5p” refers to the hsa-miR-7107-5p gene described in SEQ ID NO: 185 (miRBase Accession No. MIMAT0028111) and other species homologs or orthologs.
  • the hsa-miR-7107-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • hsa-mir-7107 miRBase Accession No. MI0022958, SEQ ID NO: 378, having a hairpin-like structure as a precursor is known.
  • hsa-miR-23a-3p gene or “hsa-miR-23a-3p” refers to the hsa-miR-23a-3p gene described in SEQ ID NO: 186 (miRBase Accession No. MIMAT0000078) and other species homologs or orthologs.
  • the hsa-miR-23a-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2001, Science, 294, p853-858.
  • “hsa-miR-23a-3p” “hsa-mir-23a” (miRBase Accession No. MI0000079, SEQ ID NO: 379) having a hairpin-like structure as a precursor is known.
  • hsa-miR-4667-5p gene or “hsa-miR-4667-5p” refers to the hsa-miR-4667-5p gene described in SEQ ID NO: 187 (miRBase Accession No. MIMAT0019743) and other species homologs or orthologs.
  • the hsa-miR-4667-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86.
  • “hsa-miR-4667-5p” “hsa-mir-4667” (miRBase Accession No. MI0017297, SEQ ID NO: 380) having a hairpin-like structure as a precursor is known.
  • hsa-miR-451a gene or “hsa-miR-451a” refers to the hsa-miR-451a gene (miRBase Accession No. MIMAT0001631) described in SEQ ID NO: 188 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-451a gene can be obtained by the method described in Altvia Y et al., 2005, Nucleic Acids Res, 33, p2697-2706.
  • hsa-miR-451a “hsa-mir-451a” (miRBase Accession No. MI0001729, SEQ ID NO: 381) having a hairpin-like structure as a precursor is known.
  • hsa-miR-3940-5p gene or “hsa-miR-3940-5p” refers to the hsa-miR-3940-5p gene described in SEQ ID NO: 189 (miRBase Accession No. MIMAT0019229) and other species homologs or orthologs.
  • the hsa-miR-3940-5p gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, 5, e10563.
  • “hsa-miR-3940-5p” is known as “hsa-mir-3940” (miRBase Accession No. MI0016597, SEQ ID NO: 382) having a hairpin-like structure as a precursor.
  • hsa-miR-8059 gene or “hsa-miR-8059” refers to the hsa-miR-8059 gene (miRBase Accession No. MIMAT0030986) described in SEQ ID NO: 190 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-8059 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, 39, p480-487.
  • “hsa-miR-8059” is known as “hsa-mir-8059” (miRBase Accession No. MI0025895, SEQ ID NO: 383) having a hairpin-like structure as a precursor.
  • hsa-miR-6813-5p gene or “hsa-miR-6813-5p” refers to the hsa-miR-6813-5p gene described in SEQ ID NO: 191 (miRBase Accession No. MIMAT0027526) and other species homologs or orthologs.
  • the hsa-miR-6813-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6813-5p” is known as “hsa-mir-6683” (miRBase Accession No. MI0022658, SEQ ID NO: 384) having a hairpin-like structure as a precursor.
  • hsa-miR-4492 gene or “hsa-miR-4492” refers to the hsa-miR-4492 gene (miRBase Accession No. MIMAT0019027) described in SEQ ID NO: 192 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4492 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • “hsa-miR-4492” is known as “hsa-mir-4492” (miRBase Accession No. MI0016854, SEQ ID NO: 385) having a hairpin-like structure as a precursor.
  • hsa-miR-4476 gene or “hsa-miR-4476” refers to the hsa-miR-4476 gene (miRBase Accession No. MIMAT0019003) described in SEQ ID NO: 193 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-4476 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • “hsa-miR-4476” is known as “hsa-mir-4476” (miRBase Accession No. MI0016828, SEQ ID NO: 386) having a hairpin-like structure as a precursor.
  • hsa-miR-6090 gene or “hsa-miR-6090” refers to the hsa-miR-6090 gene (miRBase Accession No. MIMAT0023715) described in SEQ ID NO: 194 or other biological species. Includes homologs or orthologs.
  • the hsa-miR-6090 gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev, 21, p2049-2057.
  • hsa-miR-6090 “hsa-mir-6090” (miRBase Accession No. MI0020367, SEQ ID NO: 387) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6836-3p gene or “hsa-miR-6836-3p” refers to the hsa-miR-6836-3p gene (miRBase Accession No. 6) described in SEQ ID NO: 606. MIMAT0027575) and other species homologues or orthologues are included.
  • the hsa-miR-6836-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “hsa-miR-6836-3p” is known as “hsa-mir-6683” (miRBase Accession No. MI0022682, SEQ ID NO: 615), which has a hairpin-like structure as a precursor.
  • hsa-miR-3195 gene or “hsa-miR-3195” refers to the hsa-miR-3195 gene (miRBase Accession No. MIMAT0015079) described in SEQ ID NO: 607 or other biological species. Homologs or orthologs are included.
  • the hsa-miR-3195 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685.
  • hsa-miR-3195 “hsa-mir-3195” (miRBase Accession No. MI0014240, SEQ ID NO: 616) having a hairpin-like structure as a precursor is known.
  • hsa-miR-718 gene or “hsa-miR-718” refers to the hsa-miR-718 gene (miRBase Accession No. MIMAT0012735) described in SEQ ID NO: 608 or other biological species. Homologs or orthologs are included.
  • the hsa-miR-718 gene can be obtained by the method described in Artzi S et al., 2008, BMC Bioinformatics, Vol. 9, p39.
  • “hsa-miR-718” is known as “hsa-mir-718” (miRBase Accession No. MI0012489, SEQ ID NO: 617) having a hairpin-like structure as a precursor.
  • hsa-miR-3178 gene or “hsa-miR-3178” refers to the hsa-miR-3178 gene (miRBase Accession No. MIMAT0015055) described in SEQ ID NO: 609 or other biological species. Homologs or orthologs are included.
  • the hsa-miR-3178 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685.
  • hsa-miR-3178 “hsa-mir-3178” (miRBase Accession No. MI0014212, SEQ ID NO: 618) having a hairpin-like structure as a precursor is known.
  • hsa-miR-638 gene or “hsa-miR-638” refers to the hsa-miR-638 gene (miRBase Accession No. MIMAT0003308) described in SEQ ID NO: 610 or other biological species. Homologs or orthologs are included.
  • the hsa-miR-638 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, p3687-3692.
  • “hsa-miR-638” is known as “hsa-mir-638” (miRBase Accession No. MI0003653, SEQ ID NO: 619) having a hairpin-like structure as a precursor.
  • hsa-miR-4497 gene or “hsa-miR-4497” refers to the hsa-miR-4497 gene (miRBase Accession No. MIMAT0019032) described in SEQ ID NO: 611 or other biological species. Homologs or orthologs are included.
  • the hsa-miR-4497 gene can be obtained by the method described in Jim DD et al., 2010, Blood, 116, e118-e127.
  • hsa-miR-4497 “hsa-mir-4497” (miRBase Accession No. MI0016859, SEQ ID NO: 620) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6085 gene or “hsa-miR-6085” refers to the hsa-miR-6085 gene (miRBase Accession No. MIMAT0023710) described in SEQ ID NO: 612 or other biological species. Homologs or orthologs are included.
  • the hsa-miR-6085 gene can be obtained by the method described in Voellenkle C et al., 2012, RNA, 18, p472-484.
  • hsa-miR-6085 “hsa-mir-6085” (miRBase Accession No. MI0020362, SEQ ID NO: 621) having a hairpin-like structure as a precursor is known.
  • hsa-miR-6752-5p gene or “hsa-miR-6752-5p” refers to the hsa-miR-6752-5p gene described in SEQ ID NO: 613 (miRBase Accession No. MIMAT0027404) and other species homologs or orthologs.
  • the hsa-miR-6675-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
  • “Hsa-miR-6752-5p” is known as “hsa-mir-6752” (miRBase Accession No. MI0022597, SEQ ID NO: 622) having a hairpin-like structure as a precursor.
  • hsa-miR-135a-3p gene or “hsa-miR-135a-3p” refers to the hsa-miR-135a-3p gene described in SEQ ID NO: 614 (miRBase Accession No. MIMAT0004595) and other species homologs or orthologs.
  • the hsa-miR-135a-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p735-739.
  • hsa-mir-135a miRBase Accession No. MI000052, SEQ ID NO: 623 having a hairpin-like structure as a precursor is known.
  • miRNA when mature miRNA is cleaved as a mature miRNA from an RNA precursor having a hairpin-like structure, one to several bases before or after the sequence may be cleaved or long, or base substitution may occur. And is referred to as isomiR (Morin RD. Et al., 2008, Genome Res., Vol. 18, p.610-621).
  • miRBBase Release 20 in addition to the nucleotide sequence represented by any one of SEQ ID NOs: 1 to 194 and 606 to 614, the nucleotide sequence represented by any one of SEQ ID NOs: 388 to 605 and 624 to 635 called numerous isomiRs. Variants and fragments are also shown.
  • These mutants can also be obtained as miRNA having the base sequence represented by any of SEQ ID NOs: 1 to 194 and 606 to 614. That is, SEQ ID NOs: 5, 7, 8, 9, 11, 16, 19, 20, 21, 26, 27, 28, 30, 34, 37, 38, 39, 41, 43, 45, 46, 48 of the present invention.
  • polynucleotides that are isomiRs of SEQ ID NOs: 1 to 194 and 606 to 614 registered in miRBase.
  • examples of the polynucleotide containing the nucleotide sequence represented by any of SEQ ID NOs: 1 to 194 and 606 to 614 are represented by any of the precursors SEQ ID NOs: 195 to 387 and 615 to 623, respectively.
  • a polynucleotide is mentioned.
  • the present invention makes it possible to detect colorectal cancer easily and with high accuracy.
  • This figure shows hsa-miR-3679-5p represented by SEQ ID NO: 11 generated from hsa-mir-3679 represented by SEQ ID NO: 205, and hsa-miR represented by SEQ ID NO: 78.
  • the relationship of the base sequence of ⁇ 3679-3p is shown.
  • the horizontal line in the figure shows the threshold (9.43) for discriminating both groups, optimized by Fisher's discriminant analysis.
  • FIG. 1 The expression level measurement values of hsa-miR-6726-5p (SEQ ID NO: 1) of healthy subjects (50 subjects) and colon cancer patients (16 subjects) selected as the test sample group are shown as the vertical axis. Is. The horizontal line in the figure indicates the threshold value (9.43) set for the learning sample group and discriminating both groups.
  • Left figure The measured expression level of hsa-miR-6726-5p (SEQ ID NO: 1) in healthy subjects (100, circle) and colorectal cancer patients (34, triangle) selected as the learning sample group on the horizontal axis.
  • Hsa-miR-4257 (SEQ ID NO: 2) expression level measurement values are represented on the vertical axis.
  • Hsa-miR-4257 (SEQ ID NO: 2) expression level measurement values are represented on the vertical axis.
  • Colorectal cancer target nucleic acid Using the nucleic acid probe or primer for colorectal cancer detection defined above according to the present invention, a colon for detecting the presence and / or absence of colorectal cancer or colorectal cancer cells is used.
  • Major target nucleic acids as cancer markers include hsa-miR-6726-5p, hsa-miR-4257, hsa-miR-6787-5p, hsa-miR-6780b-5p, hsa-miR-3131, hsa-miR -7108-5p, hsa-miR-1343-3p, hsa-miR-1247-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-3679-5p, hsa-miR-7461, hsa -MiR-6746-5p, hsa-miR-8072, hsa-miR-6741-5p, hsa-miR- 1908-5p, hsa-miR-6857-5p, hsa-miR-4746-3p, hsa
  • hsa-miR-1231 hsa-miR-1233-5p, hsa-miR-150-3p, hsa-miR-1225-3p, hsa- at least one selected from the group consisting of miR-92a-2-5p, hsa-miR-423-5p, hsa-miR-1268a, hsa-miR-128-2-5p and hsa-miR-24-3p
  • MiRNA can also be preferably used as a target nucleic acid.
  • hsa-miR-4697-5p hsa-miR-3197, hsa-miR-675-5p, hsa-miR-4486, hsa-miR- 7107-5p, hsa-miR-23a-3p, hsa-miR-4667-5p, hsa-miR-451a, hsa-miR-3940-5p, hsa-miR-8059, hsa-miR-6683-5p, hsa- At least one miRNA selected from the group consisting of miR-4492, hsa-miR-4476 and hsa-miR-6090 can also be preferably used as the target nucleic acid.
  • the miRNA includes, for example, a human gene containing a base sequence represented by any of SEQ ID NOs: 1 to 194 and 606 to 614 (that is, hsa-miR-6726-5p, hsa-miR-4257, hsa, respectively).
  • a preferred target nucleic acid is a human gene comprising the nucleotide sequence represented by any of SEQ ID NOs: 1 to 635, or a transcription product thereof, more preferably the transcription product, ie, miRNA, a pri-miRNA that is a precursor RNA thereof. Or pre-miRNA.
  • the first target gene is the hsa-miR-6726-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the second target gene is the hsa-miR-4257 gene, their homologues, their transcripts, or their mutants or derivatives. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the third target gene is the hsa-miR-6787-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the fourth target gene is the hsa-miR-6780b-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the fifth target gene is the hsa-miR-3131 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the sixth target gene is the hsa-miR-7108-5p gene, their homologues, their transcripts, or their mutants or derivatives. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the seventh target gene is the hsa-miR-1343-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the eighth target gene is the hsa-miR-1247-3p gene, their homologues, their transcripts, or their mutants or derivatives. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the ninth target gene is the hsa-miR-4651 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the tenth target gene is the hsa-miR-6757-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • a homologue thereof a transcription product thereof, or a mutant or derivative thereof.
  • the eleventh target gene is the hsa-miR-3679-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the twelfth target gene is the hsa-miR-7641 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the thirteenth target gene is the hsa-miR-6746-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 14th target gene is the hsa-miR-8072 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the fifteenth target gene is the hsa-miR-6741-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the sixteenth target gene is the hsa-miR-1908-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the seventeenth target gene is the hsa-miR-6857-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 18th target gene is the hsa-miR-4746-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the nineteenth target gene is the hsa-miR-744-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the twentieth target gene is the hsa-miR-4792 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 21st target gene is an hsa-miR-564 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 22nd target gene is the hsa-miR-6791-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 23rd target gene is the hsa-miR-6825-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 24th target gene is the hsa-miR-6826-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 25th target gene is the hsa-miR-4665-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the twenty-sixth target gene is the hsa-miR-4467 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 27th target gene is the hsa-miR-3188 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 28th target gene is the hsa-miR-6125 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 29th target gene is the hsa-miR-6756-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 30th target gene is the hsa-miR-1228-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the thirty-first target gene is the hsa-miR-8063 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the thirty-second target gene is the hsa-miR-8069 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 33rd target gene is the hsa-miR-6875-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 34th target gene is the hsa-miR-3185 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 35th target gene is the hsa-miR-4433b-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the thirty-sixth target gene is the hsa-miR-6687-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 37th target gene is the hsa-miR-128-1-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 38th target gene is the hsa-miR-6724-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 39th target gene is the hsa-miR-1914-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 40th target gene is the hsa-miR-1225-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 41st target gene is the hsa-miR-4419b gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the forty-second target gene is the hsa-miR-7110-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 43rd target gene is the hsa-miR-187-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 44th target gene is the hsa-miR-3184-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 45th target gene is the hsa-miR-204-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 46th target gene is the hsa-miR-5572 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 47th target gene is the hsa-miR-6729-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 48th target gene is the hsa-miR-615-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 49th target gene is the hsa-miR-6749-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 50th target gene is the hsa-miR-6515-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 51st target gene is the hsa-miR-3937 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 52nd target gene is the hsa-miR-6840-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 53rd target gene is the hsa-miR-6893-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 54th target gene is the hsa-miR-4728-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 55th target gene is the hsa-miR-6717-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 56th target gene is the hsa-miR-7113-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 57th target gene is the hsa-miR-4665-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • a homologue thereof a transcription product thereof, or a mutant or derivative thereof.
  • the 58th target gene is the hsa-miR-642b-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 59th target gene is the hsa-miR-7109-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 60th target gene is the hsa-miR-6842-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 61st target gene is the hsa-miR-4442 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 62nd target gene is the hsa-miR-4433-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 63rd target gene is the hsa-miR-4707-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 64th target gene is the hsa-miR-6126 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 65th target gene is the hsa-miR-4449 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 66th target gene is the hsa-miR-4706 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 67th target gene is the hsa-miR-1913 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 68th target gene is an hsa-miR-602 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 69th target gene is the hsa-miR-939-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 70th target gene is the hsa-miR-4695-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 71st target gene is an hsa-miR-711 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • hsa-miR-711 a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • the 72nd target gene is the hsa-miR-6816-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 73rd target gene is the hsa-miR-4632-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 74th target gene is the hsa-miR-6721-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 75th target gene is the hsa-miR-7847-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 76th target gene is the hsa-miR-6132 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 77th target gene is the hsa-miR-887-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 78th target gene is the hsa-miR-3679-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 79th target gene is the hsa-miR-6784-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 80th target gene is the hsa-miR-1249 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 81st target gene is an hsa-miR-937-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • hsa-miR-937-5p gene a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • the 82nd target gene is the hsa-miR-5195-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 83rd target gene is the hsa-miR-6732-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 84th target gene is the hsa-miR-4417 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 85th target gene is the hsa-miR-4281 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 86th target gene is the hsa-miR-4734 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 87th target gene is the hsa-miR-6766-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 88th target gene is the hsa-miR-663a gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 89th target gene is the hsa-miR-4513 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 90th target gene is the hsa-miR-6781-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 91st target gene is the hsa-miR-1227-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 92nd target gene is the hsa-miR-6845-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 93rd target gene is the hsa-miR-6798-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 94th target gene is the hsa-miR-3620-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 95th target gene is the hsa-miR-1915-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 96th target gene is an hsa-miR-4294 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 97th target gene is the hsa-miR-642a-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 98th target gene is the hsa-miR-371a-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 99th target gene is the hsa-miR-940 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 100th target gene is an hsa-miR-4450 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 101st target gene is the hsa-miR-4723-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 102nd target gene is the hsa-miR-1469 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 103rd target gene is the hsa-miR-6861-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 104th target gene is the hsa-miR-7975 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 105th target gene is the hsa-miR-6879-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 106th target gene is the hsa-miR-6802-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 107th target gene is the hsa-miR-1268b gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 108th target gene is an hsa-miR-663b gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • hsa-miR-663b gene a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • the 109th target gene is the hsa-miR-125a-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 110th target gene is the hsa-miR-2861 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 111th target gene is the hsa-miR-6088 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 112th target gene is the hsa-miR-4758-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 113th target gene is the hsa-miR-296-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 114th target gene is the hsa-miR-6738-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 115th target gene is the hsa-miR-671-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 116th target gene is the hsa-miR-4454 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 117th target gene is the hsa-miR-4516 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 118th target gene is the hsa-miR-7845-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 119th target gene is the hsa-miR-4741 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 120th target gene is the hsa-miR-92b-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 121st target gene is the hsa-miR-6695-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 122nd target gene is the hsa-miR-6805-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 123rd target gene is the hsa-miR-4725-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 124th target gene is the hsa-miR-6782-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 125th target gene is the hsa-miR-4688 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 126th target gene is the hsa-miR-6850-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 127th target gene is the hsa-miR-6777-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 128th target gene is the hsa-miR-6785-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 129th target gene is the hsa-miR-7106-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 130th target gene is the hsa-miR-3663-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 131st target gene is the hsa-miR-6131 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 132nd target gene is the hsa-miR-1915-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 133rd target gene is the hsa-miR-4532 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 134th target gene is the hsa-miR-6820-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 135th target gene is the hsa-miR-4687 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 136th target gene is the hsa-miR-4638-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 137th target gene is the hsa-miR-3656 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 138th target gene is the hsa-miR-3621 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 139th target gene is the hsa-miR-6769b-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 140th target gene is an hsa-miR-149-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 141st target gene is an hsa-miR-23b-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 142nd target gene is the hsa-miR-3135b gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 143rd target gene is the hsa-miR-6848-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 144th target gene is the hsa-miR-6769a-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 145th target gene is the hsa-miR-4327 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 146th target gene is the hsa-miR-6765-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 147th target gene is the hsa-miR-6716-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 148th target gene is the hsa-miR-6877-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 149th target gene is the hsa-miR-6727-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 150th target gene is the hsa-miR-4534 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 151st target gene is the hsa-miR-614 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 152th target gene is the hsa-miR- 1202 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 153rd target gene is the hsa-miR-575 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 154th target gene is the hsa-miR-6870-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 155th target gene is the hsa-miR-6722-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 156th target gene is the hsa-miR-7777 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 157th target gene is the hsa-miR-4649-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 158th target gene is the hsa-miR-4675 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 159th target gene is the hsa-miR-6075 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 160th target gene is an hsa-miR-6679-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 161st target gene is the hsa-miR-4271 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 162nd target gene is the hsa-miR-3196 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 163rd target gene is the hsa-miR-6803-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 164th target gene is the hsa-miR-6789-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 165th target gene is the hsa-miR-4648 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 166th target gene is the hsa-miR-4508 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 167th target gene is the hsa-miR-4749-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 168th target gene is the hsa-miR-4505 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 169th target gene is the hsa-miR-5698 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 170th target gene is the hsa-miR-1199-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 171st target gene is the hsa-miR-4763-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 172nd target gene is the hsa-miR-1231 gene, their homologues, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for colorectal cancer (Patent Document 3).
  • the 173rd target gene is the hsa-miR-1233-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • Patent Document 2 There has been known a report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 174th target gene is the hsa-miR-150-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • This gene or its transcript can serve as a marker for colorectal cancer.
  • the 175th target gene is the hsa-miR-1225-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • Patent Document 2 There has been known a report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 176th target gene is the hsa-miR-92a-2-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • This gene or its transcription product can serve as markers for colorectal cancer.
  • the 177th target gene is an hsa-miR-423-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • hsa-miR-423-5p a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • the 178th target gene is the hsa-miR-1268a gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • This gene or its transcripts can serve as markers for colorectal cancer (Patent Document 3).
  • the 179th target gene is the hsa-miR-128-2-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • a report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer Patent Document 1.
  • the 180th target gene is the hsa-miR-24-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • a report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer Patent Document 1.
  • the 181st target gene is the hsa-miR-4697-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 182nd target gene is the hsa-miR-3197 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 183rd target gene is the hsa-miR-675-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 184th target gene is the hsa-miR-4486 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 185th target gene is the hsa-miR-7107-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 186th target gene is an hsa-miR-23a-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • This gene or its transcripts can serve as markers for colorectal cancer (Patent Document 2).
  • the 187th target gene is the hsa-miR-4667-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 188th target gene is the hsa-miR-451a gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 189th target gene is the hsa-miR-3940-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 190th target gene is the hsa-miR-8059 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 191st target gene is the hsa-miR-6813-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 192nd target gene is the hsa-miR-4492 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 193rd target gene is the hsa-miR-4476 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 194th target gene is an hsa-miR-6090 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. Until now, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.
  • the 195th target gene is the hsa-miR-6836-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • a change in the expression of a gene or a transcription product thereof can be a marker for colorectal cancer.
  • the 196th target gene is the hsa-miR-3195 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • a change in the expression of a gene or a transcription product thereof can be a marker for colorectal cancer.
  • the 197th target gene is an hsa-miR-718 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • a change in the expression of a gene or a transcription product thereof can be a marker for colorectal cancer.
  • the 198th target gene is the hsa-miR-3178 gene, their homologs, their transcripts, or their mutants or derivatives. Until now, there has been no report that a change in the expression of a gene or a transcription product thereof can be a marker for colorectal cancer.
  • the 199th target gene is the hsa-miR-638 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • a change in the expression of a gene or a transcription product thereof can be a marker for colorectal cancer.
  • the 200th target gene is the hsa-miR-4497 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • a change in the expression of a gene or a transcription product thereof can be a marker for colorectal cancer.
  • the 201st target gene is the hsa-miR-6085 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • a change in the expression of a gene or a transcription product thereof can be a marker for colorectal cancer.
  • the 202nd target gene is the hsa-miR-6675-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • a change in the expression of a gene or a transcription product thereof can be a marker for colorectal cancer.
  • the 203rd target gene is the hsa-miR-135a-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
  • a change in the expression of a gene or a transcription product thereof can be a marker for colorectal cancer.
  • nucleic acid probe or primer for colorectal cancer detection a nucleic acid capable of specifically binding to a target nucleic acid as the colorectal cancer marker is a nucleic acid for detecting or diagnosing colorectal cancer, such as a nucleic acid. It can be used as a probe or primer.
  • the nucleic acid probe or primer that can be used for detecting or diagnosing colorectal cancer is a target nucleic acid as the above colorectal cancer marker, such as hsa-miR-derived from human. 6726-5p, hsa-miR-4257, hsa-miR-6787-5p, hsa-miR-6780b-5p, hsa-miR-3131, hsa-miR-7108-5p, hsa-miR-13343-3p, hsa- miR-1247-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-3679-5p, hsa-miR-7641, hsa-miR-6746-5p, hsa-miR-8072, hsa- miR-6741-5p, hsa-miR-80
  • the above target nucleic acids may increase or decrease in the expression level of the target nucleic acid depending on the type of the target nucleic acid in a subject suffering from colorectal cancer compared to a healthy subject (hereinafter referred to as “the target nucleic acid”). , Referred to as “increase / decrease”). Therefore, the nucleic acid of the present invention measures the expression level of the target nucleic acid in a body fluid derived from a subject suspected of having colorectal cancer (for example, human) and a body fluid derived from a healthy body, It can be used effectively to detect cancer.
  • the nucleic acid probe or primer that can be used in the present invention is a nucleic acid probe that can specifically bind to a polynucleotide consisting of a base sequence represented by at least one of SEQ ID NOs: 1 to 171 and 606 to 614, or SEQ ID NO: 1
  • a primer for amplifying a polynucleotide comprising a base sequence represented by at least one of ⁇ 171 and 606 to 614.
  • the nucleic acid probe or primer that can be used in the present invention is further a nucleic acid probe that can specifically bind to a polynucleotide consisting of the base sequence represented by at least one of SEQ ID NOs: 172 to 180, or of SEQ ID NOs: 172 to 180 Primers for amplifying a polynucleotide comprising the base sequence represented by at least one can be included.
  • the nucleic acid probe or primer that can be used in the present invention is further a nucleic acid probe that can specifically bind to a polynucleotide consisting of the base sequence represented by at least one of SEQ ID NOs: 181 to 194, or of SEQ ID NOs: 181 to 194
  • a primer for amplifying a polynucleotide comprising the base sequence represented by at least one can be further included.
  • the nucleic acid probe or primer includes a polynucleotide group including a base sequence represented by any of SEQ ID NOs: 1 to 635, or a base sequence in which u is t in the base sequence, and a complementary sequence thereof
  • a polynucleotide group a polynucleotide group that hybridizes with DNA consisting of a base sequence complementary to the base sequence under stringent conditions (described later), a complementary polynucleotide group thereof, and the base sequences of those polynucleotide groups It includes a combination of one or more polynucleotides selected from the group of polynucleotides containing 15 or more, preferably 17 or more consecutive bases. These polynucleotides can be used as nucleic acid probes and primers for detecting the aforementioned colon cancer marker, which is a target nucleic acid.
  • nucleic acid probes or primers that can be used in the present invention are one or more polynucleotides selected from the group consisting of the following polynucleotides (a) to (e).
  • A a polynucleotide comprising the nucleotide sequence represented by any one of SEQ ID NOs: 1 to 171 and 606 to 614, or a nucleotide sequence in which u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or 15 or more A fragment thereof containing a continuous base of
  • B a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614
  • C a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, or a nucleotide sequence in which u is t in
  • the nucleic acid probe or primer usable in the present invention is further shown in the following (f) to (j) in addition to at least one polynucleotide selected from the above polynucleotides (a) to (e).
  • a polynucleotide selected from the group consisting of polynucleotides can be included.
  • the nucleic acid probe or primer that can be used in the present invention is further shown in the following (k) to (o) in addition to at least one polynucleotide selected from the above polynucleotides (a) to (j).
  • a polynucleotide selected from the group consisting of polynucleotides can be included.
  • (K) comprising a polynucleotide consisting of the base sequence represented by any of SEQ ID NOS: 181 to 194 or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or 15 or more consecutive bases Its fragments, (L) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 181 to 194, (M) a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 181 to 194, or a nucleotide sequence in which u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or Its fragments containing 15 or more consecutive bases, (N) a polynucleotide comprising a base sequence complementary to the base sequence represented by any of SEQ ID NOS: 181 to 194, or a base sequence in which u is t in the base sequence,
  • the fragment containing 15 or more consecutive bases refers to, for example, 15 to less than the total number of bases in the sequence, 17 to less than the total number of bases in the sequence, 19 To less than the total number of bases in the sequence, etc., but not limited thereto.
  • Any of the above polynucleotides or fragments thereof used in the present invention may be DNA or RNA.
  • the above-mentioned polynucleotide that can be used in the present invention can be prepared using a general technique such as a DNA recombination technique, a PCR method, or a method using a DNA / RNA automatic synthesizer.
  • DNA recombination techniques and PCR methods are described in, for example, Ausubel et al., Current Protocols in Molecular Biology, John Willy & Sons, US (1993); Sambrook et al., Molecular Cloning A Laboratory S. The techniques described can be used.
  • hsa-miR-6726-5p Human-derived hsa-miR-6726-5p, hsa-miR-4257, hsa-miR-6787-5p, hsa-miR-6780b-5p, hsa-miR- represented by SEQ ID NOs: 1 to 194 and 606 to 614 3131, hsa-miR-7108-5p, hsa-miR-1343-3p, hsa-miR-1247-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-3679-5p, hsa- miR-7641, hsa-miR-6746-5p, hsa-miR-8072, hsa-miR-6741-5p, hsa-miR-1908-5p, hsa-miR-68
  • Such a nucleic acid probe or primer can be chemically synthesized using an automatic DNA synthesizer.
  • the phosphoramidite method is used for this synthesis, and single-stranded DNA of up to about 100 bases can be automatically synthesized by this method.
  • Automatic DNA synthesizers are commercially available from, for example, Polygen, ABI, Applied BioSystems, and the like.
  • the polynucleotide of the present invention can also be prepared by a cDNA cloning method.
  • a cDNA cloning method for example, microRNA Cloning Kit Wako can be used as the cDNA cloning technique.
  • the nucleic acid probe and primer sequences for detecting the polynucleotide comprising the nucleotide sequence represented by any of SEQ ID NOs: 1 to 194 and 606 to 614 are present in vivo as miRNA or a precursor thereof.
  • the base sequences represented by SEQ ID NO: 11 and SEQ ID NO: 78 are generated from the precursor represented by SEQ ID NO: 205, and this precursor has a hairpin-like structure as shown in FIG.
  • the base sequences represented by SEQ ID NO: 11 and SEQ ID NO: 78 have mismatch sequences with each other.
  • a completely complementary base sequence with respect to the base sequence represented by SEQ ID NO: 11 or SEQ ID NO: 78 is not naturally generated in vivo. Therefore, the nucleic acid probe and primer for detecting the base sequence represented by any of SEQ ID NOs: 1 to 194 and 606 to 614 have an artificial base sequence that does not exist in the living body.
  • Colorectal cancer detection kit or device also provides a polynucleotide that can be used as a nucleic acid probe or primer in the present invention for measuring a target nucleic acid that is a colorectal cancer marker (including mutants, fragments, A kit or device for detecting colorectal cancer comprising one or more of the following may be referred to as a polynucleotide for detection):
  • the target nucleic acid that is a colorectal cancer marker in the present invention is preferably selected from the following group 1. miR-6726-5p, miR-4257, miR-6787-5p, miR-6780b-5p, miR-3131, miR-7108-5p, miR-1343-3p, miR-1247-3p, miR-4651, miR- 6757-5p, miR-3679-5p, miR-7461, miR-6746-5p, miR-8072, miR-674-5p, miR-1908-5p, miR-6857-5p, miR-4746-3p, miR- 744-5p, miR-4792, miR-564, miR-6791-5p, miR-6825-5p, miR-6826-5p, miR-4665-3p, miR-4467, miR-3188, miR-6125, miR- 6756-5p, miR-1228-3p, miR- 063, miR-8069, miR
  • Additional target nucleic acids that may optionally be used for the measurement are selected from the following group 2: miR-1231, miR-1233-5p, miR-150-3p, miR-1225-3p, miR-92a-2- 5p, miR-423-5p, miR-1268a, miR-128-2-5p and miR-24-3p.
  • Additional target nucleic acids that can optionally be used for further measurement are selected from the following group 3: miR-4697-5p, miR-3197, miR-675-5p, miR-4486, miR-7107-5p, miR -23a-3p, miR-4667-5p, miR-451a, miR-3940-5p, miR-8059, miR-6683-5p, miR-4492, miR-4476, and miR-6090.
  • the kit or device of the present invention is a nucleic acid that can specifically bind to a target nucleic acid that is the above-mentioned colorectal cancer marker, preferably the nucleic acid probe or primer described in 2 above, specifically, the polynucleic acid described in 2 above. It includes one or more polynucleotides selected from nucleotides or variants thereof.
  • the kit or device of the present invention includes a base sequence represented by any one of SEQ ID NOs: 1 to 171 and 606 to 614, or a base sequence in which u is t in the base sequence (or A polynucleotide comprising (or consisting of) a complementary sequence thereof, a polynucleotide that hybridizes with these polynucleotides under stringent conditions, or 15 or more consecutive bases of those polynucleotide sequences. At least one or more mutants or fragments.
  • the kit or device of the present invention further comprises a polynucleotide comprising (or consisting of) the nucleotide sequence represented by any of SEQ ID NOS: 172 to 180, or a nucleotide sequence in which u is t in the nucleotide sequence, and its complement
  • a polynucleotide comprising (or consisting of) a target sequence, a polynucleotide that hybridizes with these polynucleotides under stringent conditions, or a variant or fragment comprising 15 or more consecutive bases of those polynucleotide sequences, One or more can be included.
  • the kit or device of the present invention further comprises a polynucleotide comprising (or consisting of) the base sequence represented by any of SEQ ID NOs: 181 to 194, or a base sequence in which u is t in the base sequence, and its complement
  • the fragment that can be included in the kit or device of the present invention is, for example, one or more, preferably two or more polynucleotides selected from the group consisting of the following (1) to (3).
  • the polynucleotide is a polynucleotide comprising the nucleotide sequence represented by any one of SEQ ID NOs: 1-171 and 606-614, or a nucleotide sequence in which u is t in the nucleotide sequence, its complementary A polynucleotide comprising a sequence, a polynucleotide that hybridizes with these polynucleotides under stringent conditions, or a variant containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases thereof.
  • the polynucleotide is a polynucleotide comprising a base sequence represented by any of SEQ ID NOs: 172 to 180, or a base sequence in which u is t in the base sequence, or a complementary sequence thereof. Or a polynucleotide that hybridizes with these polynucleotides under stringent conditions, or a variant containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases thereof.
  • the polynucleotide is a polynucleotide comprising the nucleotide sequence represented by any of SEQ ID NOs: 181 to 194, or a nucleotide sequence in which u is t in the nucleotide sequence, or a complementary sequence thereof. Or a polynucleotide that hybridizes with these polynucleotides under stringent conditions, or a variant containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases thereof.
  • the fragment may be a polynucleotide comprising 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases.
  • the size of a polynucleotide fragment is, for example, 15 to less than the total number of bases in the sequence, 17 to less than the total number of bases in the sequence, and 19 to less than the total number of bases in the sequence.
  • the number of bases in the range is, for example, 15 to less than the total number of bases in the sequence, 17 to less than the total number of bases in the sequence, and 19 to less than the total number of bases in the sequence. The number of bases in the range.
  • kits or device of the present invention include the SEQ ID NOs shown in Table 1 (SEQ ID NOs: 1 to 194 and 606 to 614 corresponding to the miRNA markers in the table).
  • SEQ ID NOs: 1 to 194 and 606 to 614 corresponding to the miRNA markers in the table.
  • the above polynucleotides comprising the nucleotide sequence represented are combined in the number of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more These are merely examples, and all other possible combinations are intended to be encompassed by the present invention.
  • the above-mentioned combination constituting the kit or device for discriminating colorectal cancer from a healthy body includes two of the above-mentioned polynucleotides consisting of the base sequences represented by the sequence numbers shown in Table 1. It is desirable to combine them as described above. Usually, sufficient performance can be obtained with two combinations.
  • a combination of two polynucleotides consisting of a base sequence for distinguishing colorectal cancer from a healthy body or a complementary sequence thereof the above-mentioned base sequences consisting of the base sequences represented by SEQ ID NOs: 1 to 194 and 606 to 614 Of the two combinations composed of the polynucleotides of 1), a combination comprising at least one polynucleotide consisting of a base sequence represented by SEQ ID NOs: 1 to 171 newly found is preferable.
  • SEQ ID NOs: 1 to 194 and 606 to 614 SEQ ID NOs: 5, 15, 24, 32, 38, 45, 55, 64, 96
  • More preferred is a combination comprising at least one polynucleotide comprising the nucleotide sequences represented by 97 and 162.
  • this group is preferably a combination of at least one polynucleotide selected from “cancer type-specific polynucleotide group 1” and other polynucleotides of SEQ ID NOs.
  • a combination is more preferred.
  • a combination of a plurality of polynucleotides selected from the cancer species-specific polynucleotide group 1 as a combination of cancer species-specific polynucleotides that can distinguish colorectal cancer from not only healthy subjects but also other cancers.
  • the group consisting of the polynucleotides of SEQ ID NOs: 5, 45, 57, 96 and 606 contained in the cancer type-specific polynucleotide group 1 hereinafter, this group is referred to as “cancer type-specific polynucleotide group 2”.
  • the number of combinations of the above-mentioned cancer species-specific polynucleotides is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more. However, it is more preferably a combination of 6 or more, and usually a sufficient performance can be obtained with a combination of 5 or 6.
  • sequence numbers of four or five polynucleotides selected from, but not limited to, a polynucleotide comprising the nucleotide sequence represented by SEQ ID NO: 5 or a complementary sequence thereof and a cancer type-specific polynucleotide group 1
  • a polynucleotide comprising the nucleotide sequence represented by SEQ ID NO: 5 or a complementary sequence thereof and a cancer type-specific polynucleotide group 1
  • the combination with the polynucleotide which consists of a base sequence represented by sequence number represented by these, or its complementary sequence is illustrated.
  • SEQ ID NOs: 5, 45, 57, 75, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-7847-3p, hsa-miR -3195) combination
  • SEQ ID NOs: 5, 45, 96, 606, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4294, hsa-miR-6636-3p, hsa-miR-3195) combination
  • SEQ ID NO: 5, 45, 57, 97, 115, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa -MiR-642a-3p, hsa-miR
  • sequence number of four or five polynucleotides selected from, but not limited to, a polynucleotide comprising the nucleotide sequence represented by SEQ ID NO: 45 or its complementary sequence and a cancer type-specific polynucleotide group 1
  • a polynucleotide comprising the nucleotide sequence represented by SEQ ID NO: 45 or its complementary sequence and a cancer type-specific polynucleotide group 1
  • the combination with the polynucleotide which consists of a base sequence represented by represented sequence number or its complementary sequence is illustrated.
  • SEQ ID NOs: 5, 45, 96, 606, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4294, hsa-miR-6833-3p, hsa-miR-3195 )
  • Combination (2) SEQ ID NO: 5, 45, 57, 75, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-7847-3p, hsa-miR-3195) combination (3) SEQ ID NO: 5, 45, 57, 75, 606, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa -MiR-7847-3p, hsa-miR-6
  • sequence number of four or five polynucleotides selected from, but not limited to, a polynucleotide comprising the nucleotide sequence represented by SEQ ID NO: 57 or its complementary sequence and a cancer type-specific polynucleotide group 1
  • a polynucleotide comprising the nucleotide sequence represented by SEQ ID NO: 57 or its complementary sequence and a cancer type-specific polynucleotide group 1
  • the combination with the polynucleotide which consists of a base sequence represented by represented sequence number or its complementary sequence is illustrated.
  • SEQ ID NOs: 24, 41, 57, 45, 96 (markers: hsa-miR-6826-5p, hsa-miR-4419b, hsa-miR-4665-5p, hsa-miR-204-3p, hsa-miR -4294) combination
  • SEQ ID NO: 5, 45, 57, 607, 612 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-3195, hsa-miR-6085) combination
  • SEQ ID NO: 5, 45, 57, 606, 607, 608 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa -MiR-6836-3p, hsa-miR
  • sequence number of four or five polynucleotides selected from, but not limited to, a polynucleotide comprising the nucleotide sequence represented by SEQ ID NO: 96 or a complementary sequence thereof and a cancer type-specific polynucleotide group 1
  • a polynucleotide comprising the nucleotide sequence represented by SEQ ID NO: 96 or a complementary sequence thereof and a cancer type-specific polynucleotide group 1
  • the combination with the polynucleotide which consists of a base sequence represented by represented sequence number or its complementary sequence is illustrated.
  • SEQ ID NOs: 38, 96, 606, 608, 611 (markers: hsa-miR-6724-5p, hsa-miR-4294, hsa-miR-6683-3p, hsa-miR-718, hsa-miR-4497 ) (2) SEQ ID NO: 5, 45, 57, 96, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-4294, hsa- (3) SEQ ID NOs: 38, 72, 96, 606, 608, 611 (markers: hsa-miR-6724-5p, hsa-miR-6816-5p, hsa-miR-4294, hsa-miR) -6836-3p, hsa-miR-718, hsa-
  • polynucleotide consisting of the base sequence represented by SEQ ID NO: 606 or its complementary sequence and the cancer type-specific polynucleotide group 1.
  • sequence number of three polynucleotides selected from the polynucleotide consisting of the base sequence represented by SEQ ID NO: 606 or its complementary sequence and the cancer type-specific polynucleotide group 1.
  • the combination with the polynucleotide which consists of a base sequence represented by sequence number or its complementary sequence is illustrated.
  • SEQ ID NOs: 5, 24, 45, 96, 189, 606 (markers: hsa-miR-3131, hsa-miR-6826-5p, hsa-miR-204-3p, hsa-miR-4294, hsa-miR -3940-5p, hsa-miR-6836-3p) combination
  • SEQ ID NOs: 5, 15, 45, 96, 189, 606 (markers: hsa-miR-3131, hsa-miR-6741-5p, hsa- miR-204-3p, hsa-miR-4294, hsa-miR-3940-5p, hsa-miR-6636-3p)
  • SEQ ID NO: 5, 45, 96, 189, 606, 613 (marker: hsa -MiR-3131, hsa-miR-204-3p, hsa
  • the kit or device of the present invention includes known polynucleotides that enable detection of colorectal cancer, in addition to the polynucleotides of the present invention described above (which may include mutants, fragments or derivatives). Nucleotides or polynucleotides that may be found in the future can also be included.
  • the kit of the present invention can also contain an antibody for measuring a known colorectal cancer test marker such as CEA or CA19-9.
  • the polynucleotides contained in the kit of the present invention can be individually or arbitrarily combined and packaged in different containers.
  • the kit of the present invention can include a kit for extracting nucleic acid (for example, total RNA) from body fluids, cells or tissues, a fluorescent substance for labeling, an enzyme and medium for nucleic acid amplification, instructions for use, and the like.
  • nucleic acid for example, total RNA
  • the device of the present invention is a device for measuring a cancer marker in which a nucleic acid such as a polynucleotide according to the present invention described above is bound or attached to a solid phase, for example.
  • a nucleic acid such as a polynucleotide according to the present invention described above is bound or attached to a solid phase
  • the material of the solid phase are plastic, paper, glass, silicon, and the like. From the viewpoint of ease of processing, a preferable material of the solid phase is plastic.
  • the shape of the solid phase is arbitrary, for example, a square shape, a round shape, a strip shape, a film shape and the like.
  • the device of the present invention includes, for example, a device for measurement by a hybridization technique, and specific examples include a blotting device, a nucleic acid array (for example, a microarray, a DNA chip, an RNA chip, etc.).
  • a blotting device for example, a blotting device, a nucleic acid array (for example, a microarray, a DNA chip, an RNA chip, etc.).
  • the nucleic acid array technology uses a high-density dispenser called a spotter or arrayer on the surface of a solid phase that has been subjected to surface treatment such as introduction of functional groups such as L-lysine coat, amino group, and carboxyl group as necessary.
  • the method of spotting nucleic acids the method of spraying nucleic acids onto a solid phase using an inkjet that ejects fine droplets from a nozzle with a piezoelectric element, the method of sequentially synthesizing nucleotides on a solid phase, etc.
  • an array such as a chip is produced by binding or attaching the nucleic acids one by one, and the target nucleic acid is measured using hybridization using this array.
  • the kit or device of the present invention comprises at least one, preferably at least two, more preferably at least three, most preferably at least five or all of miRNAs that are the above-mentioned group 1 colorectal cancer markers.
  • the kit or device of the present invention may further optionally contain at least one, preferably at least two, more preferably at least three, most preferably at least five miRNAs that are colorectal cancer markers of Group 2 above. Nucleic acids that can specifically bind to each of one or more to all of the polynucleotides can be included.
  • the kit or device of the present invention may further optionally contain at least one, preferably at least two, more preferably at least three, most preferably at least five of the above-mentioned group 3 colorectal cancer markers miRNA.
  • Nucleic acids that can specifically bind to each of one or more to all of the polynucleotides can be included.
  • the kit or device of the present invention can be used for the detection of the following 4 colorectal cancers.
  • the present invention further uses the kit or device of the present invention described in the above 3 (including the above-described nucleic acid that can be used in the present invention) in the following group in a sample: miR- 6726-5p, miR-4257, miR-6787-5p, miR-6780b-5p, miR-3131, miR-7108-5p, miR-13343-3p, miR-1247-3p, miR-4651, miR-6757- 5p, miR-3679-5p, miR-7641, miR-6746-5p, miR-8072, miR-6741-5p, miR-1908-5p, miR-6857-5p, miR-4746-3p, miR-744 5p, miR-4792, miR-564, miR-6791-5p, miR-6825-5p, miR-68 26-5p, miR-4665-3p, miR-4467, miR-3188, miR-6
  • the above method of the present invention enables early diagnosis of cancer with minimal invasiveness, high sensitivity and specificity, thereby leading to early treatment and improvement of prognosis, as well as monitoring disease aversion and surgical Enables monitoring of the effectiveness of radiotherapeutic and chemotherapeutic treatments.
  • RNA extraction reagent liquid sample kit (Toray Industries, Inc.)
  • a general acidic phenol method Acid Guanidinium-Phenol-Chloroform (AGPC) method
  • Trizol registered trademark
  • kits such as miRNeasy (registered trademark) Mini Kit (Qiagen) can be used, but are not limited to these methods.
  • the present invention also provides the use of the kit or device of the present invention for in vitro detection of an expression product of a colon cancer-derived miRNA gene in a specimen derived from a subject.
  • the kit or device is used as described above, and includes a single or any possible combination of polynucleotides that can be used in the present invention.
  • the polynucleotide contained in the kit or device of the present invention can be used as a probe or primer.
  • a primer Life Technologies' TaqMan (registered trademark) MicroRNA Assays, Qiagen's miScript PCR System, and the like can be used, but are not limited thereto.
  • Polynucleotides contained in the kit or device of the present invention are quantitatively determined by hybridization techniques such as Northern blotting, Southern blotting, in situ hybridization, Northern hybridization, Southern hybridization, and quantitative RT-PCR.
  • a known method for specifically detecting a specific gene such as an amplification technique, it can be used as a primer or a probe according to a conventional method.
  • body fluid such as blood, serum, plasma, urine, etc. of the subject is collected according to the type of detection method used.
  • total RNA prepared by the above-described method may be used, or various polynucleotides containing cDNA prepared based on the RNA may be used.
  • the kit or device of the present invention is useful for diagnosis of colorectal cancer or detection of the presence or absence of morbidity.
  • colorectal cancer detection using the kit or device is carried out using a sample such as blood, serum, plasma, urine or the like from a subject suspected of having colorectal cancer.
  • the detection can be performed in vitro by detecting the expression level of the gene detected by the nucleic acid probe or primer contained therein.
  • the expression level of the target miRNA marker measured by the polynucleotide is compared with their expression level in a sample such as blood, serum, plasma or urine of a healthy body. If there is a statistically significant difference, the subject can be evaluated as having colorectal cancer.
  • the method of the present invention can be combined with imaging diagnostic methods such as enema contrast examination, CT examination, MRI examination, and bone scintigraphy examination in addition to fecal occult blood, rectal examination, and colonoscopy.
  • imaging diagnostic methods such as enema contrast examination, CT examination, MRI examination, and bone scintigraphy examination in addition to fecal occult blood, rectal examination, and colonoscopy.
  • the method of the present invention can specifically detect colorectal cancer and can be substantially distinguished from cancers other than colorectal cancer.
  • a method of detecting that a sample using a kit or device of the present invention does not contain an expression product of a gene derived from colon cancer or that an expression product of a gene derived from colon cancer is contained in a subject A body fluid such as blood, serum, plasma, urine is collected, and the expression level of the target gene contained therein is determined according to one or a plurality of polynucleotides (mutants, fragments or derivatives) selected from the polynucleotide group of the present invention.
  • To detect the presence or absence of colorectal cancer or to detect colorectal cancer.
  • the colorectal cancer detection method of the present invention for example, in a colon cancer patient, when a therapeutic agent is administered for improving the disease, the presence or absence of the improvement of the disease or the degree of improvement is evaluated or diagnosed. You can also.
  • the method of the present invention includes, for example, the following steps (a), (b) and (c): (A) contacting a specimen from a subject with a polynucleotide in a kit or device of the present invention in vitro; (B) measuring the expression level of the target nucleic acid in the specimen using the polynucleotide as a nucleic acid probe or primer; (C) A step of evaluating the presence or absence of colorectal cancer (cells) in the subject based on the result of (b), Can be included.
  • the present invention relates to miR-6726-5p, miR-4257, miR-6787-5p, miR-6780b-5p, miR-3131, miR-7108-5p, miR-13343-3p, miR-1247.
  • miR-4651 miR-6757-5p, miR-3679-5p, miR-7641, miR-6746-5p, miR-8072, miR-674-5p, miR-1908-5p, miR-6857-5p MiR-4746-3p, miR-744-5p, miR-4792, miR-564, miR-6791-5p, miR-6825-5p, miR-6826-5p, miR-4665-3p, miR-4467, miR -3188, miR-6125, miR-6756-5p, miR- 228-3p, miR-8063, miR-8069, miR-6875-5p, miR-3185, miR-4433b-3p, miR-6687-5p, miR-128-1-5p, miR-6724-5p, miR- 1914-3p, miR-1225-5p, miR-4419b, miR-7110-5p, miR-187-5p, miR-3184-5p
  • evaluation is not an evaluation by a doctor but an evaluation support based on a result of an in vitro examination.
  • the target nucleic acid is specifically miR-6726-5p is hsa-miR-6726-5p and miR-4257 is hsa-miR-4257.
  • MiR-6787-5p is hsa-miR-6787-5p
  • miR-6780b-5p is hsa-miR-6780b-5p
  • miR-3131 is hsa-miR-3131
  • miR-7108-5p Is hsa-miR-7108-5p
  • miR-1343-3p is hsa-miR-1343-3p
  • miR-1247-3p is hsa-miR-1247-3p
  • miR-4651 is hsa-miR -4651 and miR-6757-5p is hsa-miR-6757-5p
  • miR-3679-5p is hsa-miR-3679-5p
  • miR-7641 is hsa-miR-7641
  • miR-6746-5p is hsa-miR-6746-5p
  • miR-8072 is hsa- miR-8072, mi
  • miR-6870-5p is hsa-miR-6870-5p
  • miR-6722-3p is hsa-miR-6722-3p
  • miR-7777 is hsa-miR-7777
  • miR- 4649-5p is hsa-miR-4649-5p
  • miR-4675 is hsa-miR-4675
  • miR-6075 is hsa-miR-6075
  • miR-679-5p is hsa-miR-6679- 5p
  • miR-4271 is hsa-miR-4271
  • miR- 196 is hsa-miR-3196
  • miR-6803-5p is hsa-miR-6803-5p
  • miR-6789-5p is hsa-miR-6789-5p
  • miR-4648 is hsa-miR- 4648
  • miR-4508 is hs
  • the nucleic acid is a polynucleotide shown in the following (a) to (e): (A) a polynucleotide comprising the nucleotide sequence represented by any one of SEQ ID NOs: 1 to 171 and 606 to 614, or a nucleotide sequence in which u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or 15 or more A fragment thereof containing a continuous base of (B) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, (C) a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, or a nucleotide sequence in which u is t in the nucleotide
  • the method of the present invention further comprises miR-1231, miR-1233-5p, miR-150-3p, miR-1225-3p, miR-92a-2-5p, miR-423-5p, miR-1268a, miR-128.
  • a nucleic acid that can specifically bind to at least one polynucleotide selected from the group consisting of -2-5p and miR-24-3p can be used.
  • such a nucleic acid has miR-1231 as hsa-miR-1231, miR-1233-5p as hsa-miR-1233-5p, and miR-150-3p as hsa-miR-150.
  • miR-1225-3p is hsa-miR-1225-3p
  • miR-92a-2-5p is hsa-miR-92a-2-5p
  • miR-423-5p is hsa-miR -423-5p
  • miR-1268a is hsa-miR-1268a
  • miR-128-2-5p is hsa-miR-128-2-5p
  • miR-24-3p is hsa-miR -24-3p.
  • such a nucleic acid is a polynucleotide shown in the following (f) to (j): (F) a polynucleotide comprising the nucleotide sequence represented by any of SEQ ID NOs: 172 to 180, or a nucleotide sequence in which u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or 15 or more consecutive bases Its fragments, including (G) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 172 to 180, (H) a polynucleotide comprising a base sequence complementary to the base sequence represented by any of SEQ ID NOs: 172 to 180, or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or Its fragments containing 15 or more consecutive bases, (I) a polynucleotide comprising a nucleotide sequence complementary
  • the nucleic acid in the method of the present invention further includes miR-4697-5p, miR-3197, miR-675-5p, miR-4486, miR-7107-5p, miR-23a-3p, miR-4667-5p, miR-451a ,
  • a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of miR-3940-5p, miR-8059, miR-6683-5p, miR-4492, miR-4476 and miR-6090 Can be used.
  • Such nucleic acids specifically include miR-4697-5p is hsa-miR-4697-5p, miR-3197 is hsa-miR-3197, and miR-675-5p is hsa-miR-675.
  • miR-4486 is hsa-miR-4486
  • miR-7107-5p is hsa-miR-7107-5p
  • miR-23a-3p is hsa-miR-23a-3p
  • miR -4667-5p is hsa-miR-4667-5p
  • miR-451a is hsa-miR-451a
  • miR-3940-5p is hsa-miR-3940-5p
  • miR-8059 is hsa-miR -8059
  • miR-6683-5p is hsa-miR-6814-5p
  • miR- 492 is hsa-miR-4492
  • miR-4476 is hsa-miR-4476
  • miR-6090 is hsa-miR-6090.
  • such a nucleic acid is a polynucleotide shown in the following (k) to (o): (K) a polynucleotide comprising the nucleotide sequence represented by any of SEQ ID NOS: 181 to 194, or a nucleotide sequence in which u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or 15 or more consecutive bases Its fragments, including (L) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 181 to 194, (M) a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 181 to 194, or a nucleotide sequence in which u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or Its fragments containing 15 or more consecutive bases, (N) a polynucleotide shown in the following
  • Specimens used in the method of the present invention include specimens prepared from a subject's biological tissue (preferably, large intestine tissue), body fluid such as blood, serum, plasma, urine and the like. Specifically, an RNA-containing sample prepared from the tissue, a sample containing a polynucleotide further prepared therefrom, a body fluid such as blood, serum, plasma, urine, a part or all of a biological tissue of a subject, a biopsy, etc. Or a biological tissue extracted by surgery, etc., from which a specimen for measurement can be prepared.
  • a subject refers to mammals such as, but not limited to, humans, monkeys, mice, rats, and the like, preferably humans.
  • the steps can be changed according to the type of specimen used as a measurement target.
  • RNA When RNA is used as the measurement object, the detection of colorectal cancer (cells) is performed, for example, by the following steps (a), (b) and (c): (A) binding RNA prepared from a specimen of a subject or a complementary polynucleotide (cDNA) transcribed therefrom to a polynucleotide in the kit or device of the present invention; (B) Measure RNA derived from a sample bound to the polynucleotide or cDNA synthesized from the RNA by hybridization using the polynucleotide as a nucleic acid probe or by quantitative RT-PCR using the polynucleotide as a primer. Step to do, (C) a step of evaluating the presence or absence of colorectal cancer (expression of derived gene) based on the measurement result of (b) above, Can be included.
  • steps (a), (b) and (c) (A) binding RNA prepared from a specimen of a subject or a complementary polyn
  • colon cancer derived gene expression
  • various hybridization methods can be used.
  • hybridization method for example, Northern blot method, Southern blot method, RT-PCR method, DNA chip analysis method, in situ hybridization method, Northern hybridization method, Southern hybridization method and the like can be used. .
  • the presence or absence of each gene in RNA and the expression level thereof can be detected and measured by using the nucleic acid probe that can be used in the present invention.
  • the nucleic acid probe (complementary strand) is labeled with a radioisotope (32P, 33P, 35S, etc.) or a fluorescent substance, and is transferred to a nylon membrane or the like according to a conventional method.
  • the signal derived from the DNA / RNA double-stranded label (radioisotope or fluorescent substance) formed after hybridization with the RNA was detected with a radiation detector (BAS-1800II (Fuji Photo Film Co., Ltd.), etc.) And a method of detecting and measuring with a fluorescence detector (STORM 865 (GE Healthcare) and the like can be exemplified).
  • RNA and the expression level thereof can be detected and measured by using the above-described primers that can be used in the present invention.
  • a pair of primers of the present invention (the cDNA described above) is prepared so that a region of each target gene can be amplified using a template prepared from RNA derived from biological tissue of a subject according to a conventional method.
  • An example is a method of detecting a double-stranded DNA obtained by hybridizing with a cDNA with a normal strand and a reverse strand that bind to the DNA and performing a PCR method by a conventional method.
  • the above PCR is performed using a primer previously labeled with a radioisotope or a fluorescent substance, the PCR product is electrophoresed on an agarose gel, and then is detected with ethidium bromide or the like.
  • a method of detecting by staining the double-stranded DNA and a method of detecting the double-stranded DNA produced by transferring it to a nylon membrane or the like according to a conventional method and hybridizing with a labeled nucleic acid probe can be included.
  • RNA chip or DNA chip in which the nucleic acid probe (single strand or double strand) of the present invention is attached to a substrate (solid phase) is used.
  • the region where the nucleic acid probe is attached is called a probe spot, and the region where the nucleic acid probe is not attached is called a blank spot.
  • a gene group immobilized on a substrate generally has a name such as a nucleic acid chip, a nucleic acid array, or a microarray, and a DNA or RNA array includes a DNA or RNA macroarray and a DNA or RNA microarray.
  • the term “chip” includes all of them.
  • 3D-Gene registered trademark
  • Human miRNA Oligo chip Toray Industries, Inc.
  • the measurement of the DNA chip is not limited.
  • an image detector Teyphoon 9410 (GE Healthcare), 3D-Gene (registered trademark) scanner (Toray Industries, Inc.) or the like is used for the signal derived from the label of the nucleic acid probe)
  • the method of detecting and measuring can be illustrated.
  • stringent conditions refers to the extent to which a nucleic acid probe is larger than other sequences as described above (eg, average of background measurements + standard error of background measurements ⁇ 2 or more). In the measurement value) of the target sequence.
  • Stringent conditions are determined by hybridization and subsequent washing conditions.
  • the hybridization conditions are not limited, but for example, 30 to 60 ° C. and 1 to 24 hours in a solution containing SSC, surfactant, formamide, dextran sulfate, blocking agent and the like.
  • 1 ⁇ SSC is an aqueous solution (pH 7.0) containing 150 mM sodium chloride and 15 mM sodium citrate, and the surfactant contains SDS (sodium dodecyl sulfate), Triton, Tween, or the like.
  • More preferable hybridization conditions include 3 to 10 ⁇ SSC and 0.1 to 1% SDS.
  • Washing conditions after hybridization include, for example, a solution containing 0.5 ⁇ SSC at 30 ° C. and 0.1% SDS, and 0.2 at 30 ° C. There may be mentioned conditions such as continuous washing with a solution containing x SSC and 0.1% SDS and a 0.05 x SSC solution at 30 ° C. It is desirable that the complementary strand maintain a hybridized state with the target positive strand even when washed under such conditions.
  • a complementary strand a strand consisting of a base sequence that is completely complementary to the target positive strand base sequence, and at least 80%, preferably at least 85%, more preferably, the strand. Examples include strands consisting of a base sequence having at least 90% or at least 95% identity, such as at least 98% or at least 99%.
  • Examples of conditions for performing PCR using the polynucleotide fragment in the kit of the present invention as a primer include, for example, a PCR buffer having a composition such as 10 mM Tris-HCL (pH 8.3), 50 mM KCL, 1 to 2 mM MgCl 2.
  • the Tm value calculated from the primer sequence +5 to 10 ° C. may be treated for 15 seconds to 1 minute.
  • TaqMan registered trademark
  • MicroRNA Assays Life Technologies
  • LNA registered trademark
  • MicroRNA PCR Exiqon
  • Ncode registered trademark
  • miRNA qRT-PCT kit A commercially available measurement kit specially devised to quantitatively measure miRNA, such as (Invitrogen) may be used.
  • Calculation of gene expression level is not limited, but, for example, Statistical analysis of gene expression microarray data (Speed T., Chapman and HalliCensusChemistralis. Et al., Blackwell publishing) can be used in the present invention.
  • a spot can be regarded as a detection spot.
  • the average value of the measured value of the blank spot can be regarded as the background, and can be subtracted from the measured value of the probe spot to obtain the gene expression level.
  • the missing value of the gene expression level is excluded from the analysis target, preferably replaced with the minimum value of the gene expression level in each DNA chip, or more preferably 0.1 from the logarithmic value of the minimum value of the gene expression level. Can be replaced with the subtracted value. Furthermore, in order to remove low-signal genes, 20% or more, preferably 50%, more preferably 80% or more of the number of measurement samples is 2 to the 6th power, preferably 2 to the 8th power, more preferably 2 to 10 Only genes having gene expression levels greater than or equal to the power can be selected for analysis. Examples of normalization of gene expression levels include, but are not limited to, global normalization and quantile normalization (Bolstad, B. M. et al., 2003, Bioinformatics, Vol. 19, p185-193).
  • the present invention also measures the expression level of a target gene or gene in a specimen derived from a subject using the detection polynucleotide, kit, device (for example, chip) of the present invention, or a combination thereof.
  • a discriminant discriminant function
  • a discriminant is created using the gene expression level of a patient-derived specimen and a healthy specimen as a teacher sample, and it is determined or evaluated that the specimen contains and / or does not contain a gene derived from colorectal cancer. Provide a method.
  • the present invention further uses a detection polynucleotide, kit, device (for example, chip), or a combination thereof of the present invention, and the specimen contains a gene derived from colorectal cancer / or a gene derived from colorectal cancer.
  • a first step of measuring in vitro the expression level of a target gene (target nucleic acid) in a plurality of specimens that are known to be determined or evaluated not containing the target gene, and the target gene obtained in the first step The second step of creating a discriminant using the measured value of the expression level of the teacher as a teacher sample, the third step of measuring the expression level of the target gene in the specimen derived from the subject in vitro as in the first step Step, substituting the measured value of the expression level of the target gene obtained in the third step into the discriminant obtained in the second step, and the result obtained from the discriminant
  • a method is provided that is detectable by a detection polynucleotide contained in a device (eg, a chip).
  • a discriminant can be created using Fisher'
  • Linear discriminant analysis is a method of discriminating group affiliation using Equation 1 as a discriminant when the boundary of grouping is a straight line or a hyperplane.
  • x is an explanatory variable
  • w is a coefficient of the explanatory variable
  • w0 is a constant term.
  • the value obtained by the discriminant is called a discriminant score, and the measured value of a newly given data set is substituted into the discriminant as an explanatory variable, and the grouping can be discriminated by the code of the discriminant score.
  • Fisher's discriminant analysis which is a type of linear discriminant analysis, is a dimension reduction method for selecting a suitable dimension for class discrimination. Focusing on the variance of synthetic variables, the variance of data with the same label is minimized. By constructing, a synthetic variable with high discriminating power is constructed (Venables, WN, et al., Modern Applied Statistics with S. Fourth edition. Springer, 2002). In Fisher's discriminant analysis, a projection direction w that maximizes Equation 2 is obtained.
  • ⁇ is the average of inputs
  • ng is the number of data belonging to class g
  • ⁇ g is the average of inputs of data belonging to class g.
  • the numerator and denominator are the inter-class variance and intra-class variance when the data is projected in the direction of the vector w, respectively, and the discriminant coefficient wi is obtained by maximizing this ratio.
  • Recognition “, Kyoritsu Shuppan (2009), Richard O. et al., Pattern Classification Second Edition, Wiley-Interscience, 2000).
  • the Mahalanobis distance is calculated by Equation 3 in consideration of data correlation, and can be used as a nonlinear discriminant analysis for discriminating a group having a close Mahalanobis distance from each group as a belonging group.
  • ⁇ is the center vector of each group
  • S ⁇ 1 is the inverse matrix of the variance-covariance matrix of that group.
  • the center vector is calculated from the explanatory variable x, and an average vector or a median vector can be used.
  • a boundary surface called a hyperplane is used to correctly classify the data set into a known grouping, with specific data items in the data set with a known grouping as explanatory variables and the grouping to be classified as an objective variable. And determine a discriminant for classifying data using the boundary surface.
  • the discriminant can determine the grouping by substituting the measured value of the newly given data set into the discriminant as an explanatory variable. Further, the discrimination result at this time may be a group to be classified, may be a probability of being classified into a group to be classified, or may be a distance from a hyperplane.
  • a method for dealing with a non-linear problem a method is known in which a feature vector is non-linearly transformed into a higher dimension and linear identification is performed in the space.
  • An expression in which the inner product of two elements in a non-linearly mapped space is expressed only by the input in the original space is called a kernel.
  • a kernel a linear kernel, RBF (Radial Basis Function) Kernel and Gaussian kernel.
  • the optimal discriminant that is, the discriminant, can be constructed only by calculating the kernel while avoiding the calculation of the features in the mapped space while actually mapping in high dimensions by the kernel (for example, Hideki Aso et al. Frontier 6 of Statistical Science, “Statistics of Pattern Recognition and Learning: New Concepts and Methods,” Iwanami Shoten (2004), Nero Christianiani et al., SVM Introduction, Kyoritsu Publishing (2008)).
  • C-support vector classification (C-SVC), a kind of SVM method, creates a hyperplane by learning with two explanatory variables to determine which group an unknown data set falls into (C. Cortes et al., 1995, Machine Learning, 20, p 273-297).
  • C-SVC discriminant An example of calculating a C-SVC discriminant that can be used in the method of the present invention is shown below.
  • all subjects are divided into two groups: colon cancer patients and healthy subjects.
  • a colorectal tissue examination can be used.
  • a data set (hereinafter referred to as “learning sample group”) composed of comprehensive gene expression levels of the two groups of serum-derived specimens is prepared, and there is a clear difference in gene expression levels between the two groups.
  • the discriminant by C-SVC is determined with the gene as the explanatory variable and the grouping as the target variable (eg, -1 and +1).
  • Equation 4 is an objective function to be optimized, where e is all input vectors, y is an objective variable, a is a Lagrange undetermined multiplier vector, Q is a positive definite matrix, and C is a parameter for adjusting the constraint condition.
  • Equation 5 is the discriminant finally obtained, and the group to which it belongs can be determined by the sign of the value obtained by the discriminant.
  • x is a support vector
  • y is a label indicating group membership
  • a is a corresponding coefficient
  • b is a constant term
  • K is a kernel function.
  • Equation 6 the RBF kernel defined by Equation 6 can be used.
  • x represents a support vector
  • ⁇ represents a kernel parameter that adjusts the complexity of the hyperplane.
  • the specimen derived from the subject contains and / or does not contain the expression of the target gene derived from colorectal cancer, or the expression level thereof is compared with the control derived from the healthy subject.
  • a neural network a k-neighbor method, a decision tree, a logistic regression analysis, or the like can be selected.
  • the method of the present invention comprises, for example, the following steps (a), (b) and (c):
  • (C) The expression level of the target gene in the specimen derived from the subject is measured using the detection polynucleotide, kit or device (for example, DNA chip) according to the present invention, and measured according to the discriminant created in (b).
  • x in the formulas 1 to 3, 5 and 6 is an explanatory variable, and a value obtained by measuring a polynucleotide selected from the polynucleotides described in Section 2 above or a fragment thereof, and the like.
  • the explanatory variable for discriminating between the colorectal cancer patient and the healthy body of the present invention is, for example, the gene expression level selected from the following (1) to (3).
  • a discriminant created from a learning sample group is used to create a discriminant.
  • the data set includes the comprehensive gene expression level of the colorectal cancer patient group, which is the learning sample group, and the comprehensive gene expression level of the healthy body group.
  • the data set includes the comprehensive gene expression level of the colorectal cancer patient group, which is the learning sample group, and the comprehensive gene expression level of the healthy body group.
  • the P value of the Whitney U test or the P value of the Wilcoxon test the magnitude of the difference in the expression level of each gene between the two groups is determined.
  • Bonferroni correction for example, by multiplying the P value obtained by the test by the number of test repetitions, that is, the number of genes used in the analysis, and comparing it with the desired significance level, the first type of error in the entire test is obtained. Probability of occurrence can be suppressed.
  • the absolute value of the median expression ratio (Fold change) of each gene expression level is calculated between the gene expression level of the colon cancer patient group and the gene expression level of the healthy group, and the discriminant You may select the gene used for the explanatory variable.
  • the ROC curve may be created using the gene expression levels of the colorectal cancer patient group and the healthy body group, and the gene used for the explanatory variable of the discriminant may be selected based on the AUROC value.
  • a discriminant that can be calculated by the above-described various methods is created using an arbitrary number of genes having a large difference in gene expression level obtained here.
  • a method of constructing a discriminant that obtains the maximum discriminating accuracy for example, a method of constructing a discriminant with any combination of genes satisfying the significance level of the P value, or a gene used to create a discriminant, gene expression There is a method in which evaluation is repeated while increasing one by one in descending order of the amount of difference (Furey TS. Et al., 2000, Bioinformatics., Vol. 16, p906-14).
  • the gene expression level of another independent colorectal cancer patient or healthy body is substituted into the explanatory variable, and the discrimination result of the group to which the independent colorectal cancer patient or healthy body belongs is calculated. That is, the diagnostic gene set that can detect more universal colorectal cancer by evaluating the discriminant constructed using the found diagnostic gene set and the diagnostic gene set in an independent sample group, and You can find a way to identify colorectal cancer.
  • the Split-sample method for evaluating the discriminating performance (generalization) of the discriminant is preferable to use the Split-sample method for evaluating the discriminating performance (generalization) of the discriminant. That is, the data set is divided into a learning sample group and a test sample group, the gene selection and the discriminant formula are made by statistical test in the learning sample group, and the test sample group is discriminated by the discriminant formula and the test sample group The accuracy, sensitivity, and specificity are calculated using the true group to which the belongs, and the discrimination performance is evaluated. On the other hand, without dividing the data set, the gene selection and discriminant formula are created by statistical test using all the samples, and the newly prepared sample is discriminated by the discriminant to improve accuracy, sensitivity, and specificity. It is also possible to calculate and evaluate the discrimination performance.
  • the present invention relates to a polynucleotide for detection or disease diagnosis useful for diagnosis and treatment of colorectal cancer, a colorectal cancer detection method using the polynucleotide, and a colorectal cancer detection kit and device containing the polynucleotide.
  • I will provide a.
  • the gene expression in serum derived from patients whose colon cancer was finally revealed by close examination such as computed tomography using contrast medium, and those derived from patients without colon cancer.
  • Any combination from one or more of the above polynucleotides based on the sequence is defined as a diagnostic gene set.
  • a discriminant is constructed using the expression level of the diagnostic gene set in a specimen derived from a colorectal cancer patient with a class I diagnosis and a specimen derived from a class II healthy subject.
  • RNA extraction from liquid sample kit was obtained from 300 ⁇ L of serum obtained from a total of 200 healthy subjects and 50 colon cancer patients, including the above-mentioned learning sample group and test sample group. Using the RNA extraction reagent in (Toray Industries, Inc.), total RNA was obtained according to the protocol defined by the company.
  • 3D-Gene (registered trademark) miRNA Labeling kit Toray was obtained from total RNA obtained from the serum of a total of 200 healthy subjects and 50 colorectal cancer patients in the above learning sample group and test sample group.
  • MiRNA was fluorescently labeled based on the protocol (ver 2.20) defined by the same company.
  • 3D-Gene Human miRNA Oligo chip (Toray Industries, Inc.) equipped with a probe having a sequence complementary to 2,555 miRNAs among miRNAs registered in miRBBase release 20 as an oligo DNA chip ), Hybridization of miRNA in total RNA with the probe on the DNA chip and washing after hybridization were performed under stringent conditions based on the protocol established by the company.
  • the DNA chip was scanned using a 3D-Gene (registered trademark) scanner (Toray Industries, Inc.), an image was acquired, and the fluorescence intensity was digitized with 3D-Gene (registered trademark) Extraction (Toray Industries, Inc.).
  • the digitized fluorescence intensity is converted into a logarithmic value with a base of 2 to obtain the gene expression level, and the blank value is subtracted.
  • the missing value is 0.1 from the logarithmic value of the minimum value of the gene expression level in each DNA chip. Replaced with the value obtained by subtracting.
  • Calculation and statistical analysis using the expressed gene expression level of miRNA are as follows: R Language 3.0.2 (R Development Core Team (2013). R: A language and environment for static computing. R Foundation for Stating URL http://www.R-project.org/) and MASS package 7.3-30 (Venables, WN & Ripley, BD (2002) Modern Applied Statistics with S. Fourth Edition, Nsp. York.ISBN 0-387-95457-0).
  • pancreatic cancer patients pancreatic cancer patients, 33 biliary tract cancer patients, 20 stomach cancer patients, 17 esophageal cancer patients, liver cancer, no cancer in other organs with informed consent.
  • Serum was collected from 20 patients and 6 patients with benign disease of the pancreaticobiliary tract using Venoject II vacuum blood collection tube VP-AS109K60 (Terumo Corporation), and cancer was observed in organs other than the large intestine in Reference Example 1.
  • the test sample group was composed of 16 patients with no colorectal cancer and 47 healthy subjects. Subsequent operations were performed in the same manner as in Reference Example 1.
  • Example 1 ⁇ Selection of genetic markers using samples from the learning sample group and evaluation method for colorectal cancer discrimination performance of a single genetic marker using samples from the test sample group>
  • a genetic marker for distinguishing colorectal cancer from a learning sample group as a healthy body is selected, and a single large intestine is selected for each of the genetic markers selected in the test sample group samples independent of the learning sample group. A method to evaluate the discrimination performance was examined.
  • the miRNA expression levels of the learning sample group and the test sample group obtained in the above reference example were combined and normalized by quantile normalization.
  • a diagnostic gene was selected using a group of learning samples.
  • 50% or more of the genes of 2 6 or more genes Only genes with expression levels were selected.
  • Bonferroni correction is performed on the P value obtained by the two-sided t-test assuming equal variance for each gene expression level, Genes satisfying p ⁇ 0.01 were obtained as genetic markers used as explanatory variables in the discriminant equation, and are listed in Table 2.
  • a gene newly found as a marker for examining the presence or absence of colorectal cancer is a polynucleotide comprising a nucleotide sequence represented by SEQ ID NOs: 1-171.
  • a discriminant for discriminating the presence or absence of colorectal cancer was created by Fisher's discriminant analysis. That is, a discriminant is created by inputting a polynucleotide consisting of the base sequence represented by any of SEQ ID NOS: 1-180 found in the learning sample group into Equation 2, and the calculated accuracy, sensitivity, and specificity are calculated. It is shown in Table 3. Table 4 shows the discriminant coefficients and constant terms at that time.
  • the accuracy, sensitivity, and specificity in the test sample group were calculated using the discriminant created above, and the discriminating performance of the selected polynucleotide was verified with an independent sample (Table 3).
  • Table 3 For example, when the measured expression level of the nucleotide sequence represented by SEQ ID NO: 1 is compared between a healthy body (100 people) and a colorectal cancer patient (34 people) in the learning sample group, the colorectal cancer patient group versus the healthy body group It was shown that the measured value of the gene expression level was significantly low (see the left side of FIG. 2), and this result was also reproducible in healthy subjects (50) and colorectal cancer patients (16) in the test sample group ( Refer to the right in FIG.
  • the measured value of the gene expression level in the colorectal cancer patient group was significantly lower ( ⁇ ) or higher (+) than in the healthy group (Table 2).
  • the accuracy of colorectal cancer detection in the test sample group was calculated using a threshold (9.43) for discriminating both groups set in the learning sample group 16 true positives, 50 true negatives, 0 false positives and 0 false negatives. From these values, 100% accuracy, 100% sensitivity, and 100% specificity were obtained as detection performance.
  • the detection performance of all the polynucleotides shown in SEQ ID NOs: 1-180 was calculated and listed in Table 3.
  • polynucleotides having a base sequence represented by SEQ ID NOs: 1, 2, 3, 10, 14, 17, 21, 23, 32, 36, 47, 59, 65, 101 are a group of test samples. All three stage 1 colorectal cancer specimens included in the above were correctly identified as colorectal cancer. Therefore, these polynucleotides can also detect early colon cancer and contribute to early diagnosis of colon cancer.
  • twelve polynucleotides having the base sequence represented by SEQ ID NOs: 1, 2, 3, 5, 7, 10, 14, 39, 46, 73, 81, 148 are difficult to detect in the fecal occult blood test. It was possible to correctly distinguish all of the upper colon cancer, ie, one cecal cancer and three ascending colon cancers in the test sample group, as colorectal cancer. Therefore, these polynucleotides can detect colorectal cancer without being limited to the site where colorectal cancer has occurred.
  • Example 2 ⁇ Evaluation method of colorectal cancer discrimination performance by a combination of a plurality of genetic markers using test sample group samples>
  • a method for evaluating colorectal cancer discrimination performance by combining the genetic markers selected in Example 1 was examined. Specifically, among the polynucleotides consisting of the base sequences represented by SEQ ID NOs: 1 to 180 selected in Example 1, a polynucleotide comprising the base sequence represented by SEQ ID NOs: 1 to 171 newly found. Fisher's discriminant analysis was performed on 16,074 combinations of two polynucleotides containing at least one expression level measurement value of any nucleotide to construct a discriminant for discriminating the presence or absence of colorectal cancer. Next, using the discriminant created above, the accuracy, sensitivity, and specificity in the test sample group were calculated, and the discriminating performance of the selected polynucleotide was verified with an independent sample.
  • the median was calculated, there were 16 true positives, 50 true negatives, 0 false positives, and 0 false negatives. From these values, the detection performance was 100% accuracy, 100% sensitivity, and 100% specificity. It was.
  • the expression level of any of the newly found polynucleotides consisting of the base sequences represented by SEQ ID NOs: 1-171 The detection performance of all two combinations including at least one measurement value was calculated. As an example, 179 combinations including the measured expression level of the polynucleotide consisting of the base sequence represented by SEQ ID NO: 1 and the detection performance thereof are shown in Table 6.
  • the measured expression level of a polynucleotide comprising the base sequences represented by SEQ ID NO: 1 and SEQ ID NO: 2, SEQ ID NO: 1 and SEQ ID NO: 3, SEQ ID NO: 1 and SEQ ID NO: 4, and SEQ ID NO: 1 and SEQ ID NO: 5 All of the combinations showed a sensitivity of 100% in the test sample group (Table 6). Further, as an example, Table 7 shows combinations of two polynucleotides having a base sequence other than SEQ ID NO: 1.
  • SEQ ID NO: 5 and 6 SEQ ID NO: 5 and 11, SEQ ID NO: 5 and 38, SEQ ID NO: 15 and 16, SEQ ID NO: 15 and 21, SEQ ID NO: 15 and 64, SEQ ID NO: 24 and 25, SEQ ID NO: 24 and 30, SEQ ID NO: 24 and 32, SEQ ID NO: 2 and 32, SEQ ID NO: 32 and 36, SEQ ID NO: 15 and 32, SEQ ID NO: 3 and 38, SEQ ID NO: 38 and 39, SEQ ID NO: 38 and 64, SEQ ID NOS: 3 and 45, SEQ ID NOS: 45 and 58, SEQ ID NOS: 45 and 64, SEQ ID NOS: 2 and 55, SEQ ID NOS: 6 and 55, SEQ ID NOS: 55 and 64, SEQ ID NOS: 2 and 64, SEQ ID NO: 4 and 64, SEQ ID NO: 2 and 96, SEQ ID NO: 7 and 96, SEQ ID NO: 96 and
  • a marker for detecting colorectal cancer can be obtained with even better sensitivity.
  • a polynucleotide consisting of a base sequence represented by SEQ ID NOs: 1 to 171 newly found out of a polynucleotide consisting of a base sequence represented by SEQ ID NOs: 1 to 180 selected in Example 1, a test was performed.
  • the expression level value measured between the healthy body group and the colorectal cancer group is obtained, and all the polyps in descending order of the P value by Student's t-test indicating the statistical significance of the difference between the groups.
  • the colorectal cancer detection sensitivity of a combination of one to a plurality of polynucleotides is increased. evaluated. That is, the order of the combination of the polynucleotides in this evaluation is the order that goes back to the order of 170, 169 from SEQ ID NO: 171 shown in Table 2.
  • the sensitivity in the test sample group was 12.5% for one polynucleotide (SEQ ID NO: 171), 18.8% for 2 polynucleotides (SEQ ID NO: 170 and 171), and 4 polynucleotides (SEQ ID NO: 171).
  • SEQ ID NO: 168-171) 25.0%, 5 polynucleotides (SEQ ID NO: 167-171) 31.2%, 7 polynucleotides (SEQ ID NO: 165-171) 37.5%, 10 87.5% of the polynucleotide (SEQ ID NO: 162-171), 100% of 20 polynucleotides (SEQ ID NO: 152-171), 100% of 30 polynucleotides (SEQ ID NO: 142-171), 100% for 80 polynucleotides (SEQ ID NOs 92-171), 100% for 170 polynucleotides (SEQ ID NOs 2-171), 171 It was 100% with a polynucleotide (SEQ ID NO: 1 to 171).
  • the combination of a plurality of polynucleotides is not limited to the combination in the order of statistical significance as described above, and any combination of a plurality of polynucleotides can be used for detection of colorectal cancer. it can.
  • Example 3 Selection of genetic markers when using all specimens and evaluation method for colorectal cancer discrimination performance of the captured genetic markers>
  • the samples of the learning sample group and the test sample group used in Example 1 and Example 2 were integrated, and all the samples were used to select genetic markers and evaluate their colorectal cancer discrimination performance. .
  • the miRNA expression levels for the serum of 50 colon cancer patients and the serum of 150 healthy subjects obtained in the above Reference Example were normalized by quantile normalization.
  • a more reliable diagnostic marker only genes having a gene expression level of 2 6 or more in 50% or more of specimens in either the colorectal cancer patient group or the healthy body group in selecting a genetic marker Selected.
  • Bonferroni correction was performed on the P value obtained by the two-sided t-test assuming equal variance for each gene expression level, A gene satisfying p ⁇ 0.01 was selected as a gene marker to be used as an explanatory variable for the discriminant and listed in Table 8.
  • the base sequences of hsa-miR-4476 and hsa-miR-6090 genes and SEQ ID NOs: 181 to 194 related thereto were found.
  • the polynucleotides shown in SEQ ID NOs: 181 to 194 also have significantly lower ( ⁇ ) or higher (+) gene measurement values in the colon cancer patient group than in the healthy body group (+ ) Results (Table 8) were obtained and these results could be verified in the test sample group. Therefore, by using the measured value of the gene expression level described in Table 8 alone or in combination with the measured value of the gene expression level described in Table 2, it was newly obtained by the method described in Example 1 and Example 2. The specimen can be discriminated.
  • Example 4 ⁇ Evaluation method for colorectal cancer-specific discrimination performance by combining multiple genetic markers using test sample group samples>
  • the learning sample group of the sample group described in Reference Example 2 was used as a target, and in the same manner as the method described in Example 1, Of gene expression levels of miRNA in serum between cancer patients and healthy subjects, pancreatic cancer patients, biliary tract cancer patients, gastric cancer patients, esophageal cancer patients, liver cancer patients, and pancreaticobiliary benign disease patients The diagnostic gene was selected.
  • a method for evaluating the colorectal cancer-specific discrimination performance by further combining the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 606-614 was examined.
  • the miRNA expression levels of the learning sample group and the test sample group obtained in Reference Example 2 above were combined and normalized by quantile normalization.
  • Fisher's discriminant analysis is performed on 1 to 6 combinations including at least one expression level measurement value of any of the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 171 and 606 to 614, A discriminant was constructed to determine the presence or absence of colorectal cancer.
  • colorectal cancer patient group is positive sample group, while healthy body group, pancreatic cancer patient group, biliary tract cancer patient group, gastric cancer patient group, esophageal cancer patient group, liver cancer patient group and pancreaticobiliary tract
  • the benign disease patient group as a negative sample group
  • the accuracy, sensitivity, and specificity of the test sample group were calculated using the discriminant created above, and the discriminating performance of the selected polynucleotide was verified with an independent sample.
  • polynucleotides comprising the nucleotide sequences represented by the above SEQ ID NOs (SEQ ID NOs: 1 to 194 and 606 to 614 corresponding to the miRNA markers in Table 1) or their complementary sequences are present in the presence or absence of colon cancer.
  • SEQ ID NOs: 1 to 194 and 606 to 614 corresponding to the miRNA markers in Table 1 or their complementary sequences are present in the presence or absence of colon cancer.
  • colorectal cancer could be specifically distinguished from other cancers.
  • examples of the polynucleotide that can specifically bind to the target marker include, for example, SEQ ID NOs: 5, 13, 15, 24, 32, 38, 41, 45, 55, 57, 64, 72, 75, 77, 96, 97, 115.
  • the number of combinations of the above-mentioned cancer species-specific polynucleotides is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more.
  • the number of discriminators can be combined, but in the combination of 6 or more, the discrimination accuracy was 90% or more.
  • Table 9-1 shows the discrimination accuracy when measured using a polynucleotide consisting of the base sequence represented by SEQ ID NO: 5 or its complementary sequence.
  • the maximum accuracy is 90.1% in the learning sample group, and in the test sample group An accuracy of 87.6% was indicated.
  • the maximum accuracy of 91.7% in the learning sample group The test sample group showed an accuracy of 88.8%.
  • the maximum accuracy is 94.0% in the learning sample group
  • the test sample group showed an accuracy of 91.2%.
  • the maximum accuracy is 95.6% in the learning sample group, The test sample group showed an accuracy of 93.6%.
  • the maximum accuracy is 96.4% in the learning sample group
  • the test sample group showed an accuracy of 94.8%.
  • the maximum accuracy of 96.9% in the learning sample group The test sample group showed an accuracy of 94.7%.
  • Table 9-2 shows the discrimination accuracy when measured using a polynucleotide consisting of the base sequence represented by SEQ ID NO: 45 or its complementary sequence.
  • the maximum accuracy is 56.7% in the learning sample group, and in the test sample group The accuracy was 55.4%.
  • the maximum accuracy in the learning sample group is 90.7%, The test sample group showed an accuracy of 88.4%.
  • the maximum accuracy is 94.0% in the learning sample group
  • the test sample group showed an accuracy of 89.6%.
  • the maximum accuracy is 95.2% in the learning sample group, The test sample group showed an accuracy of 91.6%.
  • the test sample group showed an accuracy of 94.4%.
  • the maximum accuracy of 97.6% in the learning sample group The test sample group showed an accuracy of 92.6%.
  • Table 9-3 shows the discrimination accuracy when measured using a polynucleotide consisting of the base sequence represented by SEQ ID NO: 57 or its complementary sequence.
  • the maximum accuracy is 60.2% in the learning sample group, and in the test sample group The accuracy was 60.6%.
  • the maximum accuracy is 60.8% in the learning sample group, and in the test sample group.
  • the maximum accuracy is 86.7% in the learning sample group, The test sample group showed an accuracy of 83.7%.
  • the maximum accuracy is 92.4% in the learning sample group
  • the test sample group showed an accuracy of 90.0%.
  • the maximum accuracy is 95.2% in the learning sample group, The test sample group showed an accuracy of 91.2%.
  • the maximum accuracy in the learning sample group is 96.2%
  • the test sample group showed an accuracy of 94.8%.
  • the maximum accuracy of 96.9% in the learning sample group The test sample group showed an accuracy of 93.6%.
  • the discrimination accuracy when measured using a polynucleotide consisting of the base sequence represented by SEQ ID NO: 96 or its complementary sequence is shown in Table 9-4.
  • the maximum accuracy is 57.9% in the learning sample group, and in the test sample group An accuracy of 59.4% was indicated.
  • the maximum accuracy is 85.9% in the learning sample group, The test sample group showed an accuracy of 83.7%.
  • the maximum accuracy is 92.6% in the learning sample group
  • the test sample group showed an accuracy of 90.4%.
  • the maximum accuracy is 94.4% in the learning sample group, The test sample group showed an accuracy of 91.2%.
  • the maximum accuracy is 96.0% in the learning sample group
  • the test sample group showed an accuracy of 94.0%.
  • the maximum accuracy is 96.3% in the learning sample group, The test sample group showed an accuracy of 93.6%.
  • Table 9-5 shows the discrimination accuracy when measured using a polynucleotide consisting of the base sequence represented by SEQ ID NO: 606 or its complementary sequence.
  • the maximum accuracy is 59.4% in the learning sample group, and in the test sample group The accuracy was 58.6%.
  • the maximum accuracy is 86.6% in the learning sample group, The test sample group showed an accuracy of 82.9%.
  • the maximum accuracy is 92.6% in the learning sample group
  • the test sample group showed an accuracy of 91.2%.
  • the maximum accuracy is 94.8% in the learning sample group, The test sample group showed an accuracy of 90.0%.
  • the maximum accuracy is 96.0% in the learning sample group
  • the test sample group showed an accuracy of 93.6%.
  • the maximum accuracy is 95.3% in the learning sample group, The test sample group showed an accuracy of 93.6%.
  • colorectal cancer can be detected more sensitively than existing tumor markers, so that colorectal cancer can be detected and treated at an early stage. As a result, it is possible to improve the survival rate and to provide a treatment option of endoscopic surgery with less burden on the patient.
  • colorectal cancer can be effectively detected by a simple and inexpensive method, thereby enabling early detection, diagnosis and treatment of colorectal cancer.
  • colorectal cancer can be detected minimally invasively using patient blood, so that colorectal cancer can be detected easily and quickly.
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